--- _id: '12875' abstract: - lang: eng text: The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and is composed of a rich diversity of excitatory and inhibitory neurons and glia. However, the developmental principles directing the generation of SC cell-type diversity are not understood. Here, we pursued systematic cell lineage tracing in silico and in vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal analysis with single-cell sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron types, even at the stage of terminal division. While individual clonal units show no pre-defined cellular composition, the establishment of appropriate relative proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively, our findings provide an inaugural framework at the single-RGP/-cell level of the mammalian SC ontogeny. acknowledged_ssus: - _id: Bio - _id: M-Shop - _id: LifeSc - _id: PreCl acknowledgement: "We thank Liqun Luo for his continued support, for providing essential resources for generating Fzd10-CreER mice which were generated in his laboratory, and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic mouse line for this study; A. Heger for mouse colony management; R. Beattie and T. Asenov for designing and producing components of acute slice recovery chamber for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial experiments, technical support and/or assistance. This study was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds; the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H. " article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Giselle T full_name: Cheung, Giselle T id: 471195F6-F248-11E8-B48F-1D18A9856A87 last_name: Cheung orcid: 0000-0001-8457-2572 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Thomas full_name: Krausgruber, Thomas last_name: Krausgruber - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Martin full_name: Schrammel, Martin id: f13e7cae-e8bd-11ed-841a-96dedf69f46d last_name: Schrammel - first_name: Natalie Y full_name: Özgen, Natalie Y id: e68ece33-f6e0-11ea-865d-ae1031dcc090 last_name: Özgen - first_name: Alexis full_name: Ivec, Alexis id: 1d144691-e8be-11ed-9b33-bdd3077fad4c last_name: Ivec - first_name: Christoph full_name: Bock, Christoph last_name: Bock - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Cheung GT, Pauler F, Koppensteiner P, et al. Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. 2024;112(2):230-246.e11. doi:10.1016/j.neuron.2023.11.009 apa: Cheung, G. T., Pauler, F., Koppensteiner, P., Krausgruber, T., Streicher, C., Schrammel, M., … Hippenmeyer, S. (2024). Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.11.009 chicago: Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, Thomas Krausgruber, Carmen Streicher, Martin Schrammel, Natalie Y Özgen, et al. “Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus.” Neuron. Elsevier, 2024. https://doi.org/10.1016/j.neuron.2023.11.009. ieee: G. T. Cheung et al., “Multipotent progenitors instruct ontogeny of the superior colliculus,” Neuron, vol. 112, no. 2. Elsevier, p. 230–246.e11, 2024. ista: Cheung GT, Pauler F, Koppensteiner P, Krausgruber T, Streicher C, Schrammel M, Özgen NY, Ivec A, Bock C, Shigemoto R, Hippenmeyer S. 2024. Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. 112(2), 230–246.e11. mla: Cheung, Giselle T., et al. “Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus.” Neuron, vol. 112, no. 2, Elsevier, 2024, p. 230–246.e11, doi:10.1016/j.neuron.2023.11.009. short: G.T. Cheung, F. Pauler, P. Koppensteiner, T. Krausgruber, C. Streicher, M. Schrammel, N.Y. Özgen, A. Ivec, C. Bock, R. Shigemoto, S. Hippenmeyer, Neuron 112 (2024) 230–246.e11. date_created: 2023-04-27T09:41:48Z date_published: 2024-01-17T00:00:00Z date_updated: 2024-03-05T09:43:02Z day: '17' ddc: - '570' department: - _id: SiHi - _id: RySh doi: 10.1016/j.neuron.2023.11.009 external_id: pmid: - '38096816' file: - access_level: open_access checksum: 32b3788f7085cf44a84108d8faaff3ce content_type: application/pdf creator: dernst date_created: 2024-02-06T13:56:15Z date_updated: 2024-02-06T13:56:15Z file_id: '14944' file_name: 2024_Neuron_Cheung.pdf file_size: 5942467 relation: main_file success: 1 file_date_updated: 2024-02-06T13:56:15Z has_accepted_license: '1' intvolume: ' 112' issue: '2' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 230-246.e11 pmid: 1 project: - _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E grant_number: F07805 name: Molecular Mechanisms of Neural Stem Cell Lineage Progression publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/the-pedigree-of-brain-cells/ scopus_import: '1' status: public title: Multipotent progenitors instruct ontogeny of the superior colliculus tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 112 year: '2024' ... --- _id: '15084' abstract: - lang: eng text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n 2+\r\n -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals." acknowledged_ssus: - _id: M-Shop - _id: PreCl - _id: EM-Fac acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support. article_number: e2301449121 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Hüseyin C full_name: Önal, Hüseyin C id: 4659D740-F248-11E8-B48F-1D18A9856A87 last_name: Önal orcid: 0000-0002-2771-2011 - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Utsa full_name: Roy, Utsa id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2 last_name: Roy - first_name: Yukihiro full_name: Nakamura, Yukihiro last_name: Nakamura - first_name: Tetsushi full_name: Sadakata, Tetsushi last_name: Sadakata - first_name: Makoto full_name: Sanbo, Makoto last_name: Sanbo - first_name: Masumi full_name: Hirabayashi, Masumi last_name: Hirabayashi - first_name: JeongSeop full_name: Rhee, JeongSeop last_name: Rhee - first_name: Nils full_name: Brose, Nils last_name: Brose - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. 2024;121(8). doi:10.1073/pnas.2301449121 apa: Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121 chicago: Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121. ieee: P. Koppensteiner et al., “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” Proceedings of the National Academy of Sciences, vol. 121, no. 8. Proceedings of the National Academy of Sciences, 2024. ista: Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. 121(8), e2301449121. mla: Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences, vol. 121, no. 8, e2301449121, Proceedings of the National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121. short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences 121 (2024). date_created: 2024-03-05T09:23:55Z date_published: 2024-02-20T00:00:00Z date_updated: 2024-03-12T13:44:18Z day: '20' ddc: - '570' department: - _id: RySh - _id: PeJo doi: 10.1073/pnas.2301449121 ec_funded: 1 external_id: pmid: - '38346189' file: - access_level: open_access checksum: b25b2a057c266ff317a48b0d54d6fc8a content_type: application/pdf creator: dernst date_created: 2024-03-12T13:42:42Z date_updated: 2024-03-12T13:42:42Z file_id: '15110' file_name: 2024_PNAS_Koppensteiner.pdf file_size: 13648221 relation: main_file success: 1 file_date_updated: 2024-03-12T13:42:42Z has_accepted_license: '1' intvolume: ' 121' issue: '8' language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: Proceedings of the National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/ record: - id: '13173' relation: research_data status: public status: public title: GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 121 year: '2024' ... --- _id: '14843' abstract: - lang: eng text: The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission. acknowledged_ssus: - _id: EM-Fac - _id: PreCl - _id: M-Shop acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C. article_processing_charge: No article_type: original author: - first_name: JingJing full_name: Chen, JingJing id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Itaru full_name: Arai, Itaru id: 32A73F6C-F248-11E8-B48F-1D18A9856A87 last_name: Arai - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. doi:10.1016/j.neuron.2023.12.002 apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., & Jonas, P. M. (n.d.). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002 chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, n.d. https://doi.org/10.1016/j.neuron.2023.12.002. ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” Neuron. Elsevier. ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron, Elsevier, doi:10.1016/j.neuron.2023.12.002. short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron (n.d.). date_created: 2024-01-21T23:00:56Z date_published: 2024-01-11T00:00:00Z date_updated: 2024-03-14T13:14:18Z day: '11' department: - _id: PeJo - _id: EM-Fac - _id: RySh doi: 10.1016/j.neuron.2023.12.002 ec_funded: 1 external_id: pmid: - '38215739' language: - iso: eng month: '01' oa_version: None pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5 grant_number: P36232 name: Mechanisms of GABA release in hippocampal circuits - _id: 26B66A3E-B435-11E9-9278-68D0E5697425 grant_number: '25383' name: Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse publication: Neuron publication_identifier: eissn: - 1097-4199 issn: - 0896-6273 publication_status: inpress publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/synapses-brought-to-the-point/ record: - id: '15101' relation: dissertation_contains status: public scopus_import: '1' status: public title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2024' ... --- _id: '12809' abstract: - lang: eng text: "Understanding the mechanisms of learning and memory formation has always been one of\r\nthe main goals in neuroscience. Already Pavlov (1927) in his early days has used his classic\r\nconditioning experiments to study the neural mechanisms governing behavioral adaptation.\r\nWhat was not known back then was that the part of the brain that is largely responsible for\r\nthis type of associative learning is the cerebellum.\r\nSince then, plenty of theories on cerebellar learning have emerged. Despite their differences,\r\none thing they all have in common is that learning relies on synaptic and intrinsic plasticity.\r\nThe goal of my PhD project was to unravel the molecular mechanisms underlying synaptic\r\nplasticity in two synapses that have been shown to be implicated in motor learning, in an\r\neffort to understand how learning and memory formation are processed in the cerebellum.\r\nOne of the earliest and most well-known cerebellar theories postulates that motor learning\r\nlargely depends on long-term depression at the parallel fiber-Purkinje cell (PC-PC) synapse.\r\nHowever, the discovery of other types of plasticity in the cerebellar circuitry, like long-term\r\npotentiation (LTP) at the PC-PC synapse, potentiation of molecular layer interneurons (MLIs),\r\nand plasticity transfer from the cortex to the cerebellar/ vestibular nuclei has increased the\r\npopularity of the idea that multiple sites of plasticity might be involved in learning.\r\nStill a lot remains unknown about the molecular mechanisms responsible for these types of\r\nplasticity and whether they occur during physiological learning.\r\nIn the first part of this thesis we have analyzed the variation and nanodistribution of voltagegated calcium channels (VGCCs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid\r\ntype glutamate receptors (AMPARs) on the parallel fiber-Purkinje cell synapse after vestibuloocular reflex phase reversal adaptation, a behavior that has been suggested to rely on PF-PC\r\nLTP. We have found that on the last day of adaptation there is no learning trace in form of\r\nVGCCs nor AMPARs variation at the PF-PC synapse, but instead a decrease in the number of\r\nPF-PC synapses. These data seem to support the view that learning is only stored in the\r\ncerebellar cortex in an initial learning phase, being transferred later to the vestibular nuclei.\r\nNext, we have studied the role of MLIs in motor learning using a relatively simple and well characterized behavioral paradigm – horizontal optokinetic reflex (HOKR) adaptation. We\r\nhave found behavior-induced MLI potentiation in form of release probability increase that\r\ncould be explained by the increase of VGCCs at the presynaptic side. Our results strengthen\r\nthe idea of distributed cerebellar plasticity contributing to learning and provide a novel\r\nmechanism for release probability increase. " acknowledged_ssus: - _id: EM-Fac - _id: Bio - _id: PreCl alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Catarina full_name: Alcarva, Catarina id: 3A96634C-F248-11E8-B48F-1D18A9856A87 last_name: Alcarva citation: ama: 'Alcarva C. Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. 2023. doi:10.15479/at:ista:12809' apa: 'Alcarva, C. (2023). Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12809' chicago: 'Alcarva, Catarina. “Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12809.' ieee: 'C. Alcarva, “Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning,” Institute of Science and Technology Austria, 2023.' ista: 'Alcarva C. 2023. Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. Institute of Science and Technology Austria.' mla: 'Alcarva, Catarina. Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12809.' short: 'C. Alcarva, Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning, Institute of Science and Technology Austria, 2023.' date_created: 2023-04-06T07:54:09Z date_published: 2023-04-06T00:00:00Z date_updated: 2023-04-26T12:16:56Z day: '06' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: RySh doi: 10.15479/at:ista:12809 file: - access_level: closed checksum: 35b5997d2b0acb461f9d33d073da0df5 content_type: application/pdf creator: cchlebak date_created: 2023-04-07T06:16:06Z date_updated: 2023-04-07T06:16:06Z embargo: 2024-04-07 embargo_to: open_access file_id: '12814' file_name: Thesis_CatarinaAlcarva_final pdfA.pdf file_size: 9881969 relation: main_file - access_level: closed checksum: 81198f63c294890f6d58e8b29782efdc content_type: application/pdf creator: cchlebak date_created: 2023-04-07T06:17:11Z date_updated: 2023-04-07T06:17:11Z file_id: '12815' file_name: Thesis_CatarinaAlcarva_final_for printing.pdf file_size: 44201583 relation: source_file - access_level: closed checksum: 0317bf7f457bb585f99d453ffa69eb53 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cchlebak date_created: 2023-04-07T06:18:05Z date_updated: 2023-04-07T06:18:05Z file_id: '12816' file_name: Thesis_CatarinaAlcarva_final.docx file_size: 84731244 relation: source_file file_date_updated: 2023-04-07T06:18:05Z has_accepted_license: '1' language: - iso: eng month: '04' oa_version: Published Version page: '115' project: - _id: 267DFB90-B435-11E9-9278-68D0E5697425 name: 'Plasticity in the cerebellum: Which molecular mechanisms are behind physiological learning?' publication_identifier: issn: - 2663 - 337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 title: 'Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning' type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2023' ... --- _id: '14253' abstract: - lang: eng text: Junctions between the endoplasmic reticulum (ER) and the plasma membrane (PM) are specialized membrane contacts ubiquitous in eukaryotic cells. Concentration of intracellular signaling machinery near ER-PM junctions allows these domains to serve critical roles in lipid and Ca2+ signaling and homeostasis. Subcellular compartmentalization of protein kinase A (PKA) signaling also regulates essential cellular functions, however, no specific association between PKA and ER-PM junctional domains is known. Here, we show that in brain neurons type I PKA is directed to Kv2.1 channel-dependent ER-PM junctional domains via SPHKAP, a type I PKA-specific anchoring protein. SPHKAP association with type I PKA regulatory subunit RI and ER-resident VAP proteins results in the concentration of type I PKA between stacked ER cisternae associated with ER-PM junctions. This ER-associated PKA signalosome enables reciprocal regulation between PKA and Ca2+ signaling machinery to support Ca2+ influx and excitation-transcription coupling. These data reveal that neuronal ER-PM junctions support a receptor-independent form of PKA signaling driven by membrane depolarization and intracellular Ca2+, allowing conversion of information encoded in electrical signals into biochemical changes universally recognized throughout the cell. acknowledgement: We thank Kayla Templeton and Peter Turcanu for technical assistance, Michelle Salemi for assistance with LC-MS data acquisition and analysis, Dr. Belvin Gong for advice on monoclonal antibody generation, Drs. Maria Casas Prat and Eamonn Dickson for assistance with super-resolution TIRF microscopy, Dr. Oscar Cerda for assistance with the design of TAT-FFAT peptides, Dr. Fernando Santana for helpful discussions, and Dr. Jodi Nunnari for a careful reading of our manuscript. We also thank Dr. Alan Howe, Dr. Sohum Mehta, and Dr. Jin Zhang for providing plasmids used in this study. This project was funded by NIH Grants R01NS114210 and R21NS101648 (J.S.T.), and F32NS108519 (N.C.V.). article_number: '5231' article_processing_charge: Yes article_type: original author: - first_name: Nicholas C. full_name: Vierra, Nicholas C. last_name: Vierra - first_name: Luisa full_name: Ribeiro-Silva, Luisa last_name: Ribeiro-Silva - first_name: Michael full_name: Kirmiz, Michael last_name: Kirmiz - first_name: Deborah full_name: Van Der List, Deborah last_name: Van Der List - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Olivia A. full_name: Mack, Olivia A. last_name: Mack - first_name: James full_name: Carroll, James last_name: Carroll - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Sue A. full_name: Aicher, Sue A. last_name: Aicher - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: James S. full_name: Trimmer, James S. last_name: Trimmer citation: ama: Vierra NC, Ribeiro-Silva L, Kirmiz M, et al. Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. Nature Communications. 2023;14. doi:10.1038/s41467-023-40930-6 apa: Vierra, N. C., Ribeiro-Silva, L., Kirmiz, M., Van Der List, D., Bhandari, P., Mack, O. A., … Trimmer, J. S. (2023). Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-40930-6 chicago: Vierra, Nicholas C., Luisa Ribeiro-Silva, Michael Kirmiz, Deborah Van Der List, Pradeep Bhandari, Olivia A. Mack, James Carroll, et al. “Neuronal ER-Plasma Membrane Junctions Couple Excitation to Ca2+-Activated PKA Signaling.” Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-40930-6. ieee: N. C. Vierra et al., “Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling,” Nature Communications, vol. 14. Springer Nature, 2023. ista: Vierra NC, Ribeiro-Silva L, Kirmiz M, Van Der List D, Bhandari P, Mack OA, Carroll J, Le Monnier E, Aicher SA, Shigemoto R, Trimmer JS. 2023. Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. Nature Communications. 14, 5231. mla: Vierra, Nicholas C., et al. “Neuronal ER-Plasma Membrane Junctions Couple Excitation to Ca2+-Activated PKA Signaling.” Nature Communications, vol. 14, 5231, Springer Nature, 2023, doi:10.1038/s41467-023-40930-6. short: N.C. Vierra, L. Ribeiro-Silva, M. Kirmiz, D. Van Der List, P. Bhandari, O.A. Mack, J. Carroll, E. Le Monnier, S.A. Aicher, R. Shigemoto, J.S. Trimmer, Nature Communications 14 (2023). date_created: 2023-09-03T22:01:14Z date_published: 2023-08-26T00:00:00Z date_updated: 2023-09-06T06:53:32Z day: '26' ddc: - '570' department: - _id: RySh doi: 10.1038/s41467-023-40930-6 external_id: pmid: - '37633939' file: - access_level: open_access checksum: 6ab8aab4e957f626a09a1c73db3388fb content_type: application/pdf creator: dernst date_created: 2023-09-06T06:50:07Z date_updated: 2023-09-06T06:50:07Z file_id: '14270' file_name: 2023_NatureComm_Vierra.pdf file_size: 9412549 relation: main_file success: 1 file_date_updated: 2023-09-06T06:50:07Z has_accepted_license: '1' intvolume: ' 14' language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 14 year: '2023' ... --- _id: '13202' abstract: - lang: eng text: Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an essential role in neuronal activities through interaction with various proteins involved in signaling at membranes. However, the distribution pattern of PI(4,5)P2 and the association with these proteins on the neuronal cell membranes remain elusive. In this study, we established a method for visualizing PI(4,5)P2 by SDS-digested freeze-fracture replica labeling (SDS-FRL) to investigate the quantitative nanoscale distribution of PI(4,5)P2 in cryo-fixed brain. We demonstrate that PI(4,5)P2 forms tiny clusters with a mean size of ∼1000 nm2 rather than randomly distributed in cerebellar neuronal membranes in male C57BL/6J mice. These clusters show preferential accumulation in specific membrane compartments of different cell types, in particular, in Purkinje cell (PC) spines and granule cell (GC) presynaptic active zones. Furthermore, we revealed extensive association of PI(4,5)P2 with CaV2.1 and GIRK3 across different membrane compartments, whereas its association with mGluR1α was compartment specific. These results suggest that our SDS-FRL method provides valuable insights into the physiological functions of PI(4,5)P2 in neurons. acknowledged_ssus: - _id: EM-Fac acknowledgement: This work was supported by The Institute of Science and Technology (IST) Austria, the European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. 793482 (to K.E.) and by the European Research Council (ERC) Grant Agreement No. 694539 (to R.S.). We thank Nicoleta Condruz (IST Austria, Klosterneuburg, Austria) for technical assistance with sample preparation, the Electron Microscopy Facility of IST Austria (Klosterneuburg, Austria) for technical support with EM works, Natalia Baranova (University of Vienna, Vienna, Austria) and Martin Loose (IST Austria, Klosterneuburg, Austria) for advice on liposome preparation, and Yugo Fukazawa (University of Fukui, Fukui, Japan) for comments. article_processing_charge: No article_type: original author: - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Eguchi K, Le Monnier E, Shigemoto R. Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. 2023;43(23):4197-4216. doi:10.1523/JNEUROSCI.1514-22.2023 apa: Eguchi, K., Le Monnier, E., & Shigemoto, R. (2023). Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1514-22.2023 chicago: Eguchi, Kohgaku, Elodie Le Monnier, and Ryuichi Shigemoto. “Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.” The Journal of Neuroscience. Society for Neuroscience, 2023. https://doi.org/10.1523/JNEUROSCI.1514-22.2023. ieee: K. Eguchi, E. Le Monnier, and R. Shigemoto, “Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons,” The Journal of Neuroscience, vol. 43, no. 23. Society for Neuroscience, pp. 4197–4216, 2023. ista: Eguchi K, Le Monnier E, Shigemoto R. 2023. Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. 43(23), 4197–4216. mla: Eguchi, Kohgaku, et al. “Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.” The Journal of Neuroscience, vol. 43, no. 23, Society for Neuroscience, 2023, pp. 4197–216, doi:10.1523/JNEUROSCI.1514-22.2023. short: K. Eguchi, E. Le Monnier, R. Shigemoto, The Journal of Neuroscience 43 (2023) 4197–4216. date_created: 2023-07-09T22:01:12Z date_published: 2023-06-07T00:00:00Z date_updated: 2023-10-18T07:12:47Z day: '07' ddc: - '570' department: - _id: RySh doi: 10.1523/JNEUROSCI.1514-22.2023 ec_funded: 1 external_id: isi: - '001020132100005' pmid: - '37160366' file: - access_level: open_access checksum: 70b2141870e0bf1c94fd343e18fdbc32 content_type: application/pdf creator: alisjak date_created: 2023-07-10T09:04:58Z date_updated: 2023-07-10T09:04:58Z file_id: '13205' file_name: 2023_JN_Eguchi.pdf file_size: 7794425 relation: main_file success: 1 file_date_updated: 2023-07-10T09:04:58Z has_accepted_license: '1' intvolume: ' 43' isi: 1 issue: '23' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 4197-4216 pmid: 1 project: - _id: 2659CC84-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '793482' name: 'Ultrastructural analysis of phosphoinositides in nerve terminals: distribution, dynamics and physiological roles in synaptic transmission' - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: The Journal of Neuroscience publication_identifier: eissn: - 1529-2401 issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience quality_controlled: '1' scopus_import: '1' status: public title: Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 43 year: '2023' ... --- _id: '13126' abstract: - lang: eng text: Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here, we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: LifeSc - _id: M-Shop - _id: E-Lib acknowledgement: "We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr, Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger, Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for support with obtaining human samples. We gratefully acknowledge Eder Miguel for setting up webKnossos and Marek Šuplata for computational support and hardware control. We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing, imaging and optics, preclinical, and lab support facilities, and by the Library and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources: \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual Fellowship 101026635 under the EU Horizon 2020 program (JFW)" article_processing_charge: No author: - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Danzl JG. Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” 2023. doi:10.15479/AT:ISTA:13126 apa: Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:13126 chicago: Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.’” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13126. ieee: J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales.’” Institute of Science and Technology Austria, 2023. ista: Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:13126. mla: Danzl, Johann G. Research Data for the Publication “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13126. short: J.G. Danzl, (2023). contributor: - first_name: Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska - first_name: Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Stefanickova - first_name: Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl last_name: Roessler - first_name: Thomas last_name: Czech - first_name: Romana last_name: Höftberger - first_name: Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 date_created: 2023-06-07T07:15:12Z date_published: 2023-08-04T00:00:00Z date_updated: 2024-02-21T12:18:19Z day: '04' ddc: - '610' department: - _id: JoDa - _id: SaSi - _id: GaNo - _id: PeJo - _id: Bio - _id: RySh doi: 10.15479/AT:ISTA:13126 ec_funded: 1 file: - access_level: open_access checksum: 6f18ce9b89b47ce5abeb379869ff5c49 content_type: text/plain creator: jdanzl date_created: 2023-08-04T13:19:47Z date_updated: 2023-08-04T13:19:47Z file_id: '13961' file_name: Readme_Michalska_2023.txt file_size: 541 relation: main_file success: 1 - access_level: open_access checksum: 2098e8c5285c5e86cb69075e1b5dcf39 content_type: image/tiff creator: jdanzl date_created: 2023-08-03T11:29:29Z date_updated: 2023-08-03T11:29:29Z file_id: '13482' file_name: Fig1_b_top-left.tif file_size: 64582744 relation: main_file success: 1 - 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_id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 26AA4EF2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 23889792-32DE-11EA-91FC-C7463DDC885E name: High content imaging to decode human immune cell interactions in health and allergic disease - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry publisher: Institute of Science and Technology Austria related_material: link: - description: 'Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided via an external link due to the large size (>10GB) of the datasets. ' relation: research_data url: https://pub.ista.ac.at/group_danzl/data/CATS/ record: - id: '14257' relation: used_in_publication status: public status: public title: Research data for the publication "Imaging brain tissue architecture across millimeter to nanometer scales" tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '14257' abstract: - lang: eng text: Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: LifeSc - _id: M-Shop - _id: E-Lib acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).' article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana full_name: Korinkova, Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Korinkova - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Roessler, Karl last_name: Roessler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Romana full_name: Höftberger, Romana last_name: Höftberger - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8 apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8 chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8. ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023. ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8. short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023). date_created: 2023-09-03T22:01:15Z date_published: 2023-08-31T00:00:00Z date_updated: 2024-02-21T12:18:18Z day: '31' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa - _id: Bio - _id: RySh doi: 10.1038/s41587-023-01911-8 ec_funded: 1 external_id: isi: - '001065254200001' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41587-023-01911-8 month: '08' oa: 1 oa_version: Published Version project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 23889792-32DE-11EA-91FC-C7463DDC885E name: High content imaging to decode human immune cell interactions in health and allergic disease - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry publication: Nature Biotechnology publication_identifier: eissn: - 1546-1696 issn: - 1087-0156 publication_status: epub_ahead publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/danzllab/CATS record: - id: '13126' relation: research_data status: public scopus_import: '1' status: public title: Imaging brain tissue architecture across millimeter to nanometer scales type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '13173' abstract: - lang: eng text: GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles at the presynaptic active zone (AZ). Strikingly, tonic and phasic release exhibit distinct coupling distances and are selectively affected by deletion of synaptoporin (SPO) and Ca2+-dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. Double pre-embedding immunolabeling confirmed the co-localization of CAPS2 and SPO inside the same terminal. The cytosolic protein CAPS2 showed a synaptic vesicle (SV)-associated distribution similar to the vesicular transmembrane protein SPO. A newly developed “Flash and Freeze-fracture” method revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to a persistent RRP increase. Thus, we discovered structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals. article_processing_charge: No author: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Shigemoto R. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. 2023. doi:10.15479/AT:ISTA:13173 apa: Shigemoto, R. (2023). Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:13173 chicago: Shigemoto, Ryuichi. “Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13173. ieee: R. Shigemoto, “Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals.” Institute of Science and Technology Austria, 2023. ista: Shigemoto R. 2023. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals, Institute of Science and Technology Austria, 10.15479/AT:ISTA:13173. mla: Shigemoto, Ryuichi. Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals. Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13173. short: R. Shigemoto, (2023). date_created: 2023-06-29T13:16:42Z date_published: 2023-07-29T00:00:00Z date_updated: 2024-03-12T13:44:18Z day: '29' ddc: - '571' department: - _id: RySh doi: 10.15479/AT:ISTA:13173 file: - access_level: closed checksum: ed59170869ba621f89f7c1894092192f content_type: application/x-zip-compressed creator: shigemot date_created: 2023-06-29T13:11:22Z date_updated: 2023-11-17T14:30:44Z description: After review an updated version of the data is provided file_id: '13174' file_name: Raw data for Koppensteiner et al.zip file_size: 542873672 relation: main_file title: Outdated Version - access_level: open_access checksum: c07860eb82b4d367245f1b589fe5c250 content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: patrickd date_created: 2023-11-17T14:13:02Z date_updated: 2023-11-17T14:13:02Z file_id: '14550' file_name: 11-17-23 Updated Koppensteiner et al. raw data.xlsx file_size: 915079 relation: main_file success: 1 - access_level: open_access checksum: abf84b1699edac4349dc3a92d466fb7b content_type: application/x-zip-compressed creator: dernst date_created: 2024-02-06T07:21:43Z date_updated: 2024-02-06T07:21:43Z file_id: '14942' file_name: EM_Images.zip file_size: 544868924 relation: main_file success: 1 file_date_updated: 2024-02-06T07:21:43Z has_accepted_license: '1' keyword: - medial habenula - GABAB receptor - vesicle release - Flash and Freeze - Flash and Freeze-fracture month: '07' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '15084' relation: used_in_publication status: public status: public title: Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '10890' abstract: - lang: eng text: Upon the arrival of action potentials at nerve terminals, neurotransmitters are released from synaptic vesicles (SVs) by exocytosis. CaV2.1, 2.2, and 2.3 are the major subunits of the voltage-gated calcium channel (VGCC) responsible for increasing intraterminal calcium levels and triggering SV exocytosis in the central nervous system (CNS) synapses. The two-dimensional analysis of CaV2 distributions using sodium dodecyl sulfate (SDS)-digested freeze-fracture replica labeling (SDS-FRL) has revealed their numbers, densities, and nanoscale clustering patterns in individual presynaptic active zones. The variation in these properties affects the coupling of VGCCs with calcium sensors on SVs, synaptic efficacy, and temporal precision of transmission. In this study, we summarize how the morphological parameters of CaV2 distribution obtained using SDS-FRL differ depending on the different types of synapses and could correspond to functional properties in synaptic transmission. acknowledgement: "This work was supported by the European Research Council advanced grant No. 694539 and the joint German-Austrian DFG and FWF project SYNABS (FWF: I-4638-B) to RS.\r\nThe authors thank Walter Kaufmann for his critical comments on the manuscript." article_number: '846615' article_processing_charge: No article_type: original author: - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Jacqueline-Claire full_name: Montanaro-Punzengruber, Jacqueline-Claire id: 3786AB44-F248-11E8-B48F-1D18A9856A87 last_name: Montanaro-Punzengruber - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 2022;16. doi:10.3389/fnana.2022.846615 apa: Eguchi, K., Montanaro-Punzengruber, J.-C., Le Monnier, E., & Shigemoto, R. (2022). The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.846615 chicago: Eguchi, Kohgaku, Jacqueline-Claire Montanaro-Punzengruber, Elodie Le Monnier, and Ryuichi Shigemoto. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy. Frontiers, 2022. https://doi.org/10.3389/fnana.2022.846615. ieee: K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, and R. Shigemoto, “The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals,” Frontiers in Neuroanatomy, vol. 16. Frontiers, 2022. ista: Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. 2022. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 16, 846615. mla: Eguchi, Kohgaku, et al. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy, vol. 16, 846615, Frontiers, 2022, doi:10.3389/fnana.2022.846615. short: K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, R. Shigemoto, Frontiers in Neuroanatomy 16 (2022). date_created: 2022-03-20T23:01:39Z date_published: 2022-02-24T00:00:00Z date_updated: 2023-08-03T06:07:18Z day: '24' ddc: - '570' department: - _id: RySh doi: 10.3389/fnana.2022.846615 ec_funded: 1 external_id: isi: - '000766662700001' pmid: - '35280978' file: - access_level: open_access checksum: 51ec9b90e7da919e22c01a15489eaacd content_type: application/pdf creator: dernst date_created: 2022-03-21T09:41:19Z date_updated: 2022-03-21T09:41:19Z file_id: '10911' file_name: 2022_FrontiersNeuroanatomy_Eguchi.pdf file_size: 2416395 relation: main_file success: 1 file_date_updated: 2022-03-21T09:41:19Z has_accepted_license: '1' intvolume: ' 16' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 05970B30-7A3F-11EA-A408-12923DDC885E grant_number: I04638 name: LGI1 antibody-induced pathophysiology in synapses publication: Frontiers in Neuroanatomy publication_identifier: eissn: - '16625129' publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 16 year: '2022' ... --- _id: '10889' abstract: - lang: eng text: Genetically encoded tags have introduced extensive lines of application from purification of tagged proteins to their visualization at the single molecular, cellular, histological and whole-body levels. Combined with other rapidly developing technologies such as clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, proteomics, super-resolution microscopy and proximity labeling, a large variety of genetically encoded tags have been developed in the last two decades. In this review, I focus on the current status of tag development for electron microscopic (EM) visualization of proteins with metal particle labeling. Compared with conventional immunoelectron microscopy using gold particles, tag-mediated metal particle labeling has several advantages that could potentially improve the sensitivity, spatial and temporal resolution, and applicability to a wide range of proteins of interest (POIs). It may enable researchers to detect single molecules in situ, allowing the quantitative measurement of absolute numbers and exact localization patterns of POI in the ultrastructural context. Thus, genetically encoded tags for EM could revolutionize the field as green fluorescence protein did for light microscopy, although we still have many challenges to overcome before reaching this goal. acknowledgement: European Research Council Advanced Grant (694539 to R.S.). article_processing_charge: No article_type: original author: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Shigemoto R. Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. Microscopy. 2022;71(Supplement_1):i72-i80. doi:10.1093/jmicro/dfab048 apa: Shigemoto, R. (2022). Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. Microscopy. Oxford Academic. https://doi.org/10.1093/jmicro/dfab048 chicago: Shigemoto, Ryuichi. “Electron Microscopic Visualization of Single Molecules by Tag-Mediated Metal Particle Labeling.” Microscopy. Oxford Academic, 2022. https://doi.org/10.1093/jmicro/dfab048. ieee: R. Shigemoto, “Electron microscopic visualization of single molecules by tag-mediated metal particle labeling,” Microscopy, vol. 71, no. Supplement_1. Oxford Academic, pp. i72–i80, 2022. ista: Shigemoto R. 2022. Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. Microscopy. 71(Supplement_1), i72–i80. mla: Shigemoto, Ryuichi. “Electron Microscopic Visualization of Single Molecules by Tag-Mediated Metal Particle Labeling.” Microscopy, vol. 71, no. Supplement_1, Oxford Academic, 2022, pp. i72–80, doi:10.1093/jmicro/dfab048. short: R. Shigemoto, Microscopy 71 (2022) i72–i80. date_created: 2022-03-20T23:01:39Z date_published: 2022-03-01T00:00:00Z date_updated: 2023-08-03T06:08:01Z day: '01' department: - _id: RySh doi: 10.1093/jmicro/dfab048 ec_funded: 1 external_id: isi: - '000768384100011' pmid: - '35275179' intvolume: ' 71' isi: 1 issue: Supplement_1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1093/jmicro/dfab048 month: '03' oa: 1 oa_version: Published Version page: i72-i80 pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: Microscopy publication_identifier: eissn: - 2050-5701 issn: - 2050-5698 publication_status: published publisher: Oxford Academic quality_controlled: '1' scopus_import: '1' status: public title: Electron microscopic visualization of single molecules by tag-mediated metal particle labeling type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 71 year: '2022' ... --- _id: '11419' abstract: - lang: eng text: Elevation of soluble wild-type (WT) tau occurs in synaptic compartments in Alzheimer’s disease. We addressed whether tau elevation affects synaptic transmission at the calyx of Held in slices from mice brainstem. Whole-cell loading of WT human tau (h-tau) in presynaptic terminals at 10–20 µM caused microtubule (MT) assembly and activity-dependent rundown of excitatory neurotransmission. Capacitance measurements revealed that the primary target of WT h-tau is vesicle endocytosis. Blocking MT assembly using nocodazole prevented tau-induced impairments of endocytosis and neurotransmission. Immunofluorescence imaging analyses revealed that MT assembly by WT h-tau loading was associated with an increased MT-bound fraction of the endocytic protein dynamin. A synthetic dodecapeptide corresponding to dynamin 1-pleckstrin-homology domain inhibited MT-dynamin interaction and rescued tau-induced impairments of endocytosis and neurotransmission. We conclude that elevation of presynaptic WT tau induces de novo assembly of MTs, thereby sequestering free dynamins. As a result, endocytosis and subsequent vesicle replenishment are impaired, causing activity-dependent rundown of neurotransmission. acknowledgement: We thank Yasuo Ihara, Nobuyuki Nukina, and Takeshi Sakaba for comments and Patrick Stoney for editing this paper. We also thank Shota Okuda and Mikako Matsubara for their contributions in the early stage of this study, and Satoko Wada-Kakuda for technical assistant with in vitro analysis of tau. This research was supported by funding from Okinawa Institute of Science and Technology and from Technology (OIST) and Core Research for the Evolutional Science and Technology of Japan Science and Technology Agency (CREST) to TT, and by Scientific Research on Innovative Areas to TM (Brain Protein Aging and Dementia Control 26117004). article_number: e73542 article_processing_charge: No article_type: original author: - first_name: Tetsuya full_name: Hori, Tetsuya last_name: Hori - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Han Ying full_name: Wang, Han Ying last_name: Wang - first_name: Tomohiro full_name: Miyasaka, Tomohiro last_name: Miyasaka - first_name: Laurent full_name: Guillaud, Laurent last_name: Guillaud - first_name: Zacharie full_name: Taoufiq, Zacharie last_name: Taoufiq - first_name: Satyajit full_name: Mahapatra, Satyajit last_name: Mahapatra - first_name: Hiroshi full_name: Yamada, Hiroshi last_name: Yamada - first_name: Kohji full_name: Takei, Kohji last_name: Takei - first_name: Tomoyuki full_name: Takahashi, Tomoyuki last_name: Takahashi citation: ama: Hori T, Eguchi K, Wang HY, et al. Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model. eLife. 2022;11. doi:10.7554/eLife.73542 apa: Hori, T., Eguchi, K., Wang, H. Y., Miyasaka, T., Guillaud, L., Taoufiq, Z., … Takahashi, T. (2022). Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.73542 chicago: Hori, Tetsuya, Kohgaku Eguchi, Han Ying Wang, Tomohiro Miyasaka, Laurent Guillaud, Zacharie Taoufiq, Satyajit Mahapatra, Hiroshi Yamada, Kohji Takei, and Tomoyuki Takahashi. “Microtubule Assembly by Tau Impairs Endocytosis and Neurotransmission via Dynamin Sequestration in Alzheimer’s Disease Synapse Model.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/eLife.73542. ieee: T. Hori et al., “Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model,” eLife, vol. 11. eLife Sciences Publications, 2022. ista: Hori T, Eguchi K, Wang HY, Miyasaka T, Guillaud L, Taoufiq Z, Mahapatra S, Yamada H, Takei K, Takahashi T. 2022. Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model. eLife. 11, e73542. mla: Hori, Tetsuya, et al. “Microtubule Assembly by Tau Impairs Endocytosis and Neurotransmission via Dynamin Sequestration in Alzheimer’s Disease Synapse Model.” ELife, vol. 11, e73542, eLife Sciences Publications, 2022, doi:10.7554/eLife.73542. short: T. Hori, K. Eguchi, H.Y. Wang, T. Miyasaka, L. Guillaud, Z. Taoufiq, S. Mahapatra, H. Yamada, K. Takei, T. Takahashi, ELife 11 (2022). date_created: 2022-05-29T22:01:54Z date_published: 2022-05-05T00:00:00Z date_updated: 2023-08-03T07:15:49Z day: '05' ddc: - '616' department: - _id: RySh doi: 10.7554/eLife.73542 external_id: isi: - '000876231600001' pmid: - '35471147 ' file: - access_level: open_access checksum: ccddbd167e00ff8375f12998af497152 content_type: application/pdf creator: cchlebak date_created: 2022-05-30T08:09:16Z date_updated: 2022-05-30T08:09:16Z file_id: '11421' file_name: elife-73542-v2.pdf file_size: 2466296 relation: main_file success: 1 file_date_updated: 2022-05-30T08:09:16Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer's disease synapse model tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2022' ... --- _id: '12212' abstract: - lang: eng text: Alzheimer’s disease (AD) is characterized by a reorganization of brain activity determining network hyperexcitability and loss of synaptic plasticity. Precisely, a dysfunction in metabotropic GABAB receptor signalling through G protein-gated inwardly rectifying K+ (GIRK or Kir3) channels on the hippocampus has been postulated. Thus, we determined the impact of amyloid-β (Aβ) pathology in GIRK channel density, subcellular distribution, and its association with GABAB receptors in hippocampal CA1 pyramidal neurons from the APP/PS1 mouse model using quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL) and proximity ligation in situ assay (P-LISA). In wild type mice, single SDS-FRL detection revealed a similar dendritic gradient for GIRK1 and GIRK2 in CA1 pyramidal cells, with higher densities in spines, and GIRK3 showed a lower and uniform distribution. Double SDS-FRL showed a co-clustering of GIRK2 and GIRK1 in post- and presynaptic compartments, but not for GIRK2 and GIRK3. Likewise, double GABAB1 and GIRK2 SDS-FRL detection displayed a high degree of co-clustering in nanodomains (40–50 nm) mostly in spines and axon terminals. In APP/PS1 mice, the density of GIRK2 and GIRK1, but not for GIRK3, was significantly reduced along the neuronal surface of CA1 pyramidal cells and in axon terminals contacting them. Importantly, GABAB1 and GIRK2 co-clustering was not present in APP/PS1 mice. Similarly, P-LISA experiments revealed a significant reduction in GABAB1 and GIRK2 interaction on the hippocampus of this animal model. Overall, our results provide compelling evidence showing a significant reduction on the cell surface density of pre- and postsynaptic GIRK1 and GIRK2, but not GIRK3, and a decline in GABAB receptors and GIRK2 channels co-clustering in hippocampal pyramidal neurons from APP/PS1 mice, thus suggesting that a disruption in the GABAB receptor–GIRK channel membrane assembly causes dysregulation in the GABAB signalling via GIRK channels in this AD animal model. acknowledgement: "We thank Ms. Diane Latawiec for the English revision of the manuscript. Funding sources were the Spanish Ministerio de Economía y Competitividad, Junta de Comunidades de Castilla-La Mancha (Spain), and Life Science Innovation Center at University of Fukui. We thank Centres de Recerca de Catalunya (CERCA) Programme/Generalitat de Catalunya for IDIBELL institutional support. We thank Hitoshi Takagi and Takako Maegawa at the University of Fukui for their technical assistance on SDS-FRL experiments.\r\nThis work was supported by grants from the Spanish Ministerio de Economía y Competitividad (BFU2015-63769-R, RTI2018-095812-B-I00, and PID2021-125875OB-I00) and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) to RL, Life Science Innovation Center at University of Fukui and JSPS KAKENHI (Grant Numbers 16H04662, 19H03323, and 20H05058) to YF, and Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha to AMB." article_number: '136' article_processing_charge: No article_type: original author: - first_name: Alejandro full_name: Martín-Belmonte, Alejandro last_name: Martín-Belmonte - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Rocío full_name: Alfaro-Ruiz, Rocío last_name: Alfaro-Ruiz - first_name: Ana Esther full_name: Moreno-Martínez, Ana Esther last_name: Moreno-Martínez - first_name: Luis full_name: de la Ossa, Luis last_name: de la Ossa - first_name: Ester full_name: Aso, Ester last_name: Aso - first_name: Laura full_name: Gómez-Acero, Laura last_name: Gómez-Acero - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Francisco full_name: Ciruela, Francisco last_name: Ciruela - first_name: Rafael full_name: Luján, Rafael last_name: Luján citation: ama: Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, et al. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. 2022;14. doi:10.1186/s13195-022-01078-5 apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruiz, R., Moreno-Martínez, A. E., de la Ossa, L., Aso, E., … Luján, R. (2022). Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. Springer Nature. https://doi.org/10.1186/s13195-022-01078-5 chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruiz, Ana Esther Moreno-Martínez, Luis de la Ossa, Ester Aso, Laura Gómez-Acero, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” Alzheimer’s Research & Therapy. Springer Nature, 2022. https://doi.org/10.1186/s13195-022-01078-5. ieee: A. Martín-Belmonte et al., “Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice,” Alzheimer’s Research & Therapy, vol. 14. Springer Nature, 2022. ista: Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, Moreno-Martínez AE, de la Ossa L, Aso E, Gómez-Acero L, Shigemoto R, Fukazawa Y, Ciruela F, Luján R. 2022. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. 14, 136. mla: Martín-Belmonte, Alejandro, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” Alzheimer’s Research & Therapy, vol. 14, 136, Springer Nature, 2022, doi:10.1186/s13195-022-01078-5. short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruiz, A.E. Moreno-Martínez, L. de la Ossa, E. Aso, L. Gómez-Acero, R. Shigemoto, Y. Fukazawa, F. Ciruela, R. Luján, Alzheimer’s Research & Therapy 14 (2022). date_created: 2023-01-16T09:45:51Z date_published: 2022-09-21T00:00:00Z date_updated: 2023-08-04T09:23:10Z day: '21' ddc: - '570' department: - _id: RySh doi: 10.1186/s13195-022-01078-5 external_id: isi: - '000857985500001' file: - access_level: open_access checksum: 88e49715ad6a1abf0fdb27efd65368dc content_type: application/pdf creator: dernst date_created: 2023-01-27T07:53:18Z date_updated: 2023-01-27T07:53:18Z file_id: '12413' file_name: 2022_AlzheimersResearch_MartinBelmont.pdf file_size: 11013325 relation: main_file success: 1 file_date_updated: 2023-01-27T07:53:18Z has_accepted_license: '1' intvolume: ' 14' isi: 1 keyword: - Cognitive Neuroscience - Neurology (clinical) - Neurology language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: Alzheimer's Research & Therapy publication_identifier: issn: - 1758-9193 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 14 year: '2022' ... --- _id: '11333' abstract: - lang: eng text: Adenosine triphosphate (ATP) is the energy source for various biochemical processes and biomolecular motors in living things. Development of ATP antagonists and their stimuli-controlled actions offer a novel approach to regulate biological processes. Herein, we developed azobenzene-based photoswitchable ATP antagonists for controlling the activity of motor proteins; cytoplasmic and axonemal dyneins. The new ATP antagonists showed reversible photoswitching of cytoplasmic dynein activity in an in vitro dynein-microtubule system due to the trans and cis photoisomerization of their azobenzene segment. Importantly, our ATP antagonists reversibly regulated the axonemal dynein motor activity for the force generation in a demembranated model of Chlamydomonas reinhardtii. We found that the trans and cis isomers of ATP antagonists significantly differ in their affinity to the ATP binding site. article_number: e202200807 article_processing_charge: No article_type: original author: - first_name: Sampreeth full_name: Thayyil, Sampreeth last_name: Thayyil - first_name: Yukinori full_name: Nishigami, Yukinori last_name: Nishigami - first_name: Muhammad J full_name: Islam, Muhammad J id: C94881D2-008F-11EA-8E08-2637E6697425 last_name: Islam - first_name: P. K. full_name: Hashim, P. K. last_name: Hashim - first_name: Ken'Ya full_name: Furuta, Ken'Ya last_name: Furuta - first_name: Kazuhiro full_name: Oiwa, Kazuhiro last_name: Oiwa - first_name: Jian full_name: Yu, Jian last_name: Yu - first_name: Min full_name: Yao, Min last_name: Yao - first_name: Toshiyuki full_name: Nakagaki, Toshiyuki last_name: Nakagaki - first_name: Nobuyuki full_name: Tamaoki, Nobuyuki last_name: Tamaoki citation: ama: Thayyil S, Nishigami Y, Islam MJ, et al. Dynamic control of microbial movement by photoswitchable ATP antagonists. Chemistry - A European Journal. 2022;28(30). doi:10.1002/chem.202200807 apa: Thayyil, S., Nishigami, Y., Islam, M. J., Hashim, P. K., Furuta, K., Oiwa, K., … Tamaoki, N. (2022). Dynamic control of microbial movement by photoswitchable ATP antagonists. Chemistry - A European Journal. Wiley. https://doi.org/10.1002/chem.202200807 chicago: Thayyil, Sampreeth, Yukinori Nishigami, Muhammad J Islam, P. K. Hashim, Ken’Ya Furuta, Kazuhiro Oiwa, Jian Yu, Min Yao, Toshiyuki Nakagaki, and Nobuyuki Tamaoki. “Dynamic Control of Microbial Movement by Photoswitchable ATP Antagonists.” Chemistry - A European Journal. Wiley, 2022. https://doi.org/10.1002/chem.202200807. ieee: S. Thayyil et al., “Dynamic control of microbial movement by photoswitchable ATP antagonists,” Chemistry - A European Journal, vol. 28, no. 30. Wiley, 2022. ista: Thayyil S, Nishigami Y, Islam MJ, Hashim PK, Furuta K, Oiwa K, Yu J, Yao M, Nakagaki T, Tamaoki N. 2022. Dynamic control of microbial movement by photoswitchable ATP antagonists. Chemistry - A European Journal. 28(30), e202200807. mla: Thayyil, Sampreeth, et al. “Dynamic Control of Microbial Movement by Photoswitchable ATP Antagonists.” Chemistry - A European Journal, vol. 28, no. 30, e202200807, Wiley, 2022, doi:10.1002/chem.202200807. short: S. Thayyil, Y. Nishigami, M.J. Islam, P.K. Hashim, K. Furuta, K. Oiwa, J. Yu, M. Yao, T. Nakagaki, N. Tamaoki, Chemistry - A European Journal 28 (2022). date_created: 2022-04-24T22:01:44Z date_published: 2022-05-25T00:00:00Z date_updated: 2023-10-03T10:58:31Z day: '25' department: - _id: RySh doi: 10.1002/chem.202200807 external_id: isi: - '000781658800001' pmid: - '35332959' intvolume: ' 28' isi: 1 issue: '30' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1002/chem.202200807 month: '05' oa: 1 oa_version: Published Version pmid: 1 publication: Chemistry - A European Journal publication_identifier: eissn: - '15213765' issn: - '09476539' publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: Dynamic control of microbial movement by photoswitchable ATP antagonists type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 28 year: '2022' ... --- _id: '11393' abstract: - lang: eng text: "AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and their role is\r\nimplicated in complex processes such as learning and memory and various neurological\r\ndiseases. These receptors are composed of different subunits and the subunit composition can\r\naffect channel properties, receptor trafficking and interaction with other associated proteins.\r\nUsing the high sensitivity SDS-digested freeze-fracture replica labeling (SDS-FRL) for\r\nelectron microscopy I investigated the number, density, and localization of AMPAR subunits,\r\nGluA1, GluA2, GluA3, and GluA1-3 (panAMPA) in pyramidal cells in the CA1 area of mouse\r\nhippocampus. I have found that the immunogold labeling for all of these subunits in the\r\npostsynaptic sites was highest in stratum radiatum and lowest in stratum lacunosummoleculare. The labeling density for the all subunits in the extrasynaptic sites showed a gradual\r\nincrease from the pyramidal cell soma towards the distal part of stratum radiatum. The densities\r\nof extrasynaptic GluA1, GluA2 and panAMPA labeling reached 10-15% of synaptic densities,\r\nwhile the ratio of extrasynaptic labeling for GluA3 was significantly lower compared than those\r\nfor other subunits. The labeling patterns for GluA1, GluA2 and GluA1-3 are similar and their\r\ndensities were higher in the periphery than center of synapses. In contrast, the GluA3-\r\ncontaining receptors were more centrally localized compared to the GluA1- and GluA2-\r\ncontaining receptors.\r\nThe hippocampus plays a central role in learning and memory. Contextual learning has been\r\nshown to require the delivery of AMPA receptors to CA1 synapses in the dorsal hippocampus.\r\nHowever, proximodistal heterogeneity of this plasticity and particular contribution of different\r\nAMPA receptor subunits are not fully understood. By combining inhibitory avoidance task, a\r\nhippocampus-dependent contextual fear-learning paradigm, with SDS-FRL, I have revealed an\r\nincrease in synaptic density specific to GluA1-containing AMPA receptors in the CA1 area.\r\nThe intrasynaptic distribution of GluA1 also changed from the periphery to center-preferred\r\npattern. Furthermore, this synaptic plasticity was evident selectively in stratum radiatum but\r\nnot stratum oriens, and in the CA1 subregion proximal but not distal to CA2. These findings\r\nfurther contribute to our understanding of how specific hippocampal subregions and AMPA\r\nreceptor subunits are involved in physiological learning.\r\nAlthough the immunolabeling results above shed light on subunit-specific plasticity in\r\nAMPAR distribution, no tools to visualize and study the subunit composition at the single\r\nchannel level in situ have been available. Electron microscopy with conventional immunogold\r\nlabeling approaches has limitations in the single channel analysis because of the large size of\r\nantibodies and steric hindrance hampering multiple subunit labeling of single channels. I\r\nmanaged to develop a new chemical labeling system using a short peptide tag and small\r\nsynthetic probes, which form specific covalent bond with a cysteine residue in the tag fused to\r\nproteins of interest (reactive tag system). I additionally made substantial progress into adapting\r\nthis system for AMPA receptor subunits." acknowledged_ssus: - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Marijo full_name: Jevtic, Marijo id: 4BE3BC94-F248-11E8-B48F-1D18A9856A87 last_name: Jevtic citation: ama: Jevtic M. Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus. 2022. doi:10.15479/at:ista:11393 apa: Jevtic, M. (2022). Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11393 chicago: Jevtic, Marijo. “Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11393. ieee: M. Jevtic, “Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus,” Institute of Science and Technology Austria, 2022. ista: Jevtic M. 2022. Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus. Institute of Science and Technology Austria. mla: Jevtic, Marijo. Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11393. short: M. Jevtic, Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus, Institute of Science and Technology Austria, 2022. date_created: 2022-05-17T08:57:41Z date_published: 2022-05-16T00:00:00Z date_updated: 2023-09-07T14:53:44Z day: '16' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: RySh doi: 10.15479/at:ista:11393 file: - access_level: closed checksum: 8fc695d88020d70d231dad0e9f10b138 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cchlebak date_created: 2022-05-17T09:08:06Z date_updated: 2023-05-17T22:30:03Z embargo_to: open_access file_id: '11395' file_name: MJ thesis.docx file_size: 56427603 relation: source_file - access_level: open_access checksum: c1dd20a1aece521b3500607b00e463d6 content_type: application/pdf creator: cchlebak date_created: 2022-05-17T12:09:25Z date_updated: 2023-05-17T22:30:03Z embargo: 2023-05-16 file_id: '11397' file_name: MJ_thesis_PDFA.pdf file_size: 4351981 relation: main_file file_date_updated: 2023-05-17T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '108' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7391' relation: part_of_dissertation status: public status: public supervisor: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 title: Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2022' ... --- _id: '7551' abstract: - lang: eng text: Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty. acknowledgement: We thank Peter Jonas and Peter Somogyi for critically reading the manuscript, Satoshi Kida for helpful discussion, Taijia Makinen for providing the Prox1-creERT2 mouse line, and Hiromu Yawo for the VAMP2-Venus construct. We also thank Vivek Jayaraman, Ph.D.; Rex A. Kerr, Ph.D.; Douglas S. Kim, Ph.D.; Loren L. Looger, Ph.D.; and Karel Svoboda, Ph.D. from the GENIE Project, Janelia Farm Research Campus, Howard Hughes Medical Institute for the viral constructs used for GCaMP6s expression. We also thank Jacqueline Montanaro, Vanessa Zheden, David Kleindienst, and Laura Burnett for technical assistance, as well as Robert Beattie for imaging assistance. This work was supported by a European Research Council Advanced Grant 694539 to R.S. article_processing_charge: No article_type: original author: - first_name: Felipe A full_name: Fredes Tolorza, Felipe A id: 384825DA-F248-11E8-B48F-1D18A9856A87 last_name: Fredes Tolorza - first_name: Maria A full_name: Silva Sifuentes, Maria A id: 371B3D6E-F248-11E8-B48F-1D18A9856A87 last_name: Silva Sifuentes - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner - first_name: Kenta full_name: Kobayashi, Kenta last_name: Kobayashi - first_name: Maximilian A full_name: Jösch, Maximilian A id: 2BD278E6-F248-11E8-B48F-1D18A9856A87 last_name: Jösch orcid: 0000-0002-3937-1330 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. 2021;31(1):P25-38.E5. doi:10.1016/j.cub.2020.09.074 apa: Fredes Tolorza, F. A., Silva Sifuentes, M. A., Koppensteiner, P., Kobayashi, K., Jösch, M. A., & Shigemoto, R. (2021). Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. Elsevier. https://doi.org/10.1016/j.cub.2020.09.074 chicago: Fredes Tolorza, Felipe A, Maria A Silva Sifuentes, Peter Koppensteiner, Kenta Kobayashi, Maximilian A Jösch, and Ryuichi Shigemoto. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” Current Biology. Elsevier, 2021. https://doi.org/10.1016/j.cub.2020.09.074. ieee: F. A. Fredes Tolorza, M. A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M. A. Jösch, and R. Shigemoto, “Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation,” Current Biology, vol. 31, no. 1. Elsevier, p. P25–38.E5, 2021. ista: Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. 2021. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. 31(1), P25–38.E5. mla: Fredes Tolorza, Felipe A., et al. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” Current Biology, vol. 31, no. 1, Elsevier, 2021, p. P25–38.E5, doi:10.1016/j.cub.2020.09.074. short: F.A. Fredes Tolorza, M.A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M.A. Jösch, R. Shigemoto, Current Biology 31 (2021) P25–38.E5. date_created: 2020-02-28T10:56:18Z date_published: 2021-01-11T00:00:00Z date_updated: 2023-08-04T10:47:11Z day: '11' ddc: - '570' department: - _id: MaJö - _id: RySh doi: 10.1016/j.cub.2020.09.074 ec_funded: 1 external_id: isi: - '000614361000020' file: - access_level: open_access checksum: b7b9c8bc84a08befce365c675229a7d1 content_type: application/pdf creator: dernst date_created: 2020-10-19T13:31:28Z date_updated: 2020-10-19T13:31:28Z file_id: '8678' file_name: 2021_CurrentBiology_Fredes.pdf file_size: 4915964 relation: main_file success: 1 file_date_updated: 2020-10-19T13:31:28Z has_accepted_license: '1' intvolume: ' 31' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: P25-38.E5 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: Current Biology publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/remembering-novelty/ status: public title: Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 31 year: '2021' ... --- _id: '9330' abstract: - lang: eng text: In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density. acknowledged_ssus: - _id: EM-Fac acknowledgement: "We thank Arnold Schwartz for providing α2δ-1 knockout mice; Ariane Benedetti, Sabine Baumgartner, Sandra Demetz, and Irene Mahlknecht for technical support; Nadine Ortner and Andreas Lieb for electrophysiological experiments; the team of the Electron Microscopy Facility at the Institute of Science and Technology Austria for technical support related to ultrastructural analysis; Hermann Dietrich and Anja Beierfuß and her team for animal care; Jutta Engel and Jörg Striessnig for critical discussions; and Bruno Benedetti and Bernhard Flucher for critical discussions and reading the manuscript. This study was supported by Austrian Science Fund Grants P24079, F44060, F44150, and DOC30-B30 (to G.J.O.) and T855 (to M.C.), European Research Council Grant AdG 694539 (to R.S.), Deutsche Forschungsgemeinschaft\r\nGrant SFB1348-TP A03 (to M.M.), and Interdisziplinäre Zentrum für Klinische Forschung Münster Grant Mi3/004/19 (to M.M.). This work is part of the PhD theses of C.L.S., S.M.G., and C.A." article_processing_charge: No article_type: original author: - first_name: Clemens L. full_name: Schöpf, Clemens L. last_name: Schöpf - first_name: Cornelia full_name: Ablinger, Cornelia last_name: Ablinger - first_name: Stefanie M. full_name: Geisler, Stefanie M. last_name: Geisler - first_name: Ruslan I. full_name: Stanika, Ruslan I. last_name: Stanika - first_name: Marta full_name: Campiglio, Marta last_name: Campiglio - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Benedikt full_name: Nimmervoll, Benedikt last_name: Nimmervoll - first_name: Bettina full_name: Schlick, Bettina last_name: Schlick - first_name: Johannes full_name: Brockhaus, Johannes last_name: Brockhaus - first_name: Markus full_name: Missler, Markus last_name: Missler - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Gerald J. full_name: Obermair, Gerald J. last_name: Obermair citation: ama: Schöpf CL, Ablinger C, Geisler SM, et al. Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. 2021;118(14). doi:10.1073/pnas.1920827118 apa: Schöpf, C. L., Ablinger, C., Geisler, S. M., Stanika, R. I., Campiglio, M., Kaufmann, W., … Obermair, G. J. (2021). Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1920827118 chicago: Schöpf, Clemens L., Cornelia Ablinger, Stefanie M. Geisler, Ruslan I. Stanika, Marta Campiglio, Walter Kaufmann, Benedikt Nimmervoll, et al. “Presynaptic Α2δ Subunits Are Key Organizers of Glutamatergic Synapses.” PNAS. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.1920827118. ieee: C. L. Schöpf et al., “Presynaptic α2δ subunits are key organizers of glutamatergic synapses,” PNAS, vol. 118, no. 14. National Academy of Sciences, 2021. ista: Schöpf CL, Ablinger C, Geisler SM, Stanika RI, Campiglio M, Kaufmann W, Nimmervoll B, Schlick B, Brockhaus J, Missler M, Shigemoto R, Obermair GJ. 2021. Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. 118(14). mla: Schöpf, Clemens L., et al. “Presynaptic Α2δ Subunits Are Key Organizers of Glutamatergic Synapses.” PNAS, vol. 118, no. 14, National Academy of Sciences, 2021, doi:10.1073/pnas.1920827118. short: C.L. Schöpf, C. Ablinger, S.M. Geisler, R.I. Stanika, M. Campiglio, W. Kaufmann, B. Nimmervoll, B. Schlick, J. Brockhaus, M. Missler, R. Shigemoto, G.J. Obermair, PNAS 118 (2021). date_created: 2021-04-18T22:01:40Z date_published: 2021-04-06T00:00:00Z date_updated: 2023-08-08T13:08:47Z day: '06' ddc: - '570' department: - _id: EM-Fac - _id: RySh doi: 10.1073/pnas.1920827118 ec_funded: 1 external_id: isi: - '000637398300002' file: - access_level: open_access checksum: dd014f68ae9d7d8d8fc4139a24e04506 content_type: application/pdf creator: dernst date_created: 2021-04-19T10:10:56Z date_updated: 2021-04-19T10:10:56Z file_id: '9340' file_name: 2021_PNAS_Schoepf.pdf file_size: 2603911 relation: main_file success: 1 file_date_updated: 2021-04-19T10:10:56Z has_accepted_license: '1' intvolume: ' 118' isi: 1 issue: '14' language: - iso: eng month: '04' oa: 1 oa_version: Published Version project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: PNAS publication_identifier: eissn: - 1091-6490 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' scopus_import: '1' status: public title: Presynaptic α2δ subunits are key organizers of glutamatergic synapses tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 118 year: '2021' ... --- _id: '9641' abstract: - lang: eng text: At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation. acknowledgement: This work was supported by a European Research Council Advanced Grant 694539 to Ryuichi Shigemoto. article_number: '107486' article_processing_charge: No article_type: original author: - first_name: Felipe full_name: Fredes, Felipe last_name: Fredes - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Fredes F, Shigemoto R. The role of hippocampal mossy cells in novelty detection. Neurobiology of Learning and Memory. 2021;183. doi:10.1016/j.nlm.2021.107486 apa: Fredes, F., & Shigemoto, R. (2021). The role of hippocampal mossy cells in novelty detection. Neurobiology of Learning and Memory. Elsevier. https://doi.org/10.1016/j.nlm.2021.107486 chicago: Fredes, Felipe, and Ryuichi Shigemoto. “The Role of Hippocampal Mossy Cells in Novelty Detection.” Neurobiology of Learning and Memory. Elsevier, 2021. https://doi.org/10.1016/j.nlm.2021.107486. ieee: F. Fredes and R. Shigemoto, “The role of hippocampal mossy cells in novelty detection,” Neurobiology of Learning and Memory, vol. 183. Elsevier, 2021. ista: Fredes F, Shigemoto R. 2021. The role of hippocampal mossy cells in novelty detection. Neurobiology of Learning and Memory. 183, 107486. mla: Fredes, Felipe, and Ryuichi Shigemoto. “The Role of Hippocampal Mossy Cells in Novelty Detection.” Neurobiology of Learning and Memory, vol. 183, 107486, Elsevier, 2021, doi:10.1016/j.nlm.2021.107486. short: F. Fredes, R. Shigemoto, Neurobiology of Learning and Memory 183 (2021). date_created: 2021-07-11T22:01:16Z date_published: 2021-06-30T00:00:00Z date_updated: 2023-08-10T14:10:37Z day: '30' ddc: - '610' department: - _id: RySh doi: 10.1016/j.nlm.2021.107486 ec_funded: 1 external_id: isi: - '000677694900004' pmid: - '34214666' file: - access_level: open_access checksum: 8e8298a9e8c7df146ad23f32c2a63929 content_type: application/pdf creator: cziletti date_created: 2021-07-19T13:46:06Z date_updated: 2021-07-19T13:46:06Z file_id: '9694' file_name: 2021_NeurobLearnMemory_Fredes.pdf file_size: 1994793 relation: main_file success: 1 file_date_updated: 2021-07-19T13:46:06Z has_accepted_license: '1' intvolume: ' 183' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: Neurobiology of Learning and Memory publication_identifier: eissn: - '10959564' issn: - '10747427' publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: The role of hippocampal mossy cells in novelty detection tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 183 year: '2021' ... --- _id: '10051' abstract: - lang: eng text: 'Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated Ca2+ channels (CaV), it is considered to be a central organizer of the topography of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2 knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs) with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics during high-frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by superresolution light and electron microscopy revealed an impaired topography of presynaptic CaV and a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in BCs of RIM-BP2-deficient mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmits auditory information at rates of up to hundreds of Hertz with submillisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+ influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+ channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization.' acknowledgement: This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through the Collaborative Sensory Research Center 1286 [to C.W. (A4) and T.M. (B5)] and under Germany’s Excellence Strategy Grant EXC 2067/1-390729940. We thank S. Gerke, A.J. Goldak, and C. Senger-Freitag for expert technical assistance; G. Hoch for developing image analysis routines; and S. Chepurwar and N. Strenzke for technical support and discussion regarding in vivo experiments. We also thank Dr. Christian Rosenmund, Dr. Katharina Grauel, and Dr. Stephan Sigrist for providing RIM-BP2 KO mice and Dr. Masahiko Watanabe for providing the anti-neurexin-antibody, and Dr. Toshihisa Ohtsuka for the anti-ELKS-antibody. J. Neef for help with the STED imaging and image analysis; E. Neher and S. Rizzoli for discussion and comments on the manuscript; K. Eguchi for help with the statistical analysis; and C. H. Huang and J. Neef for constant support and scientific discussion. article_processing_charge: No article_type: original author: - first_name: Tanvi full_name: Butola, Tanvi last_name: Butola - first_name: Theocharis full_name: Alvanos, Theocharis last_name: Alvanos - first_name: Anika full_name: Hintze, Anika last_name: Hintze - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Carolin full_name: Wichmann, Carolin last_name: Wichmann - first_name: Tobias full_name: Moser, Tobias last_name: Moser citation: ama: Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 2021;41(37):7742-7767. doi:10.1523/JNEUROSCI.0586-21.2021 apa: Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto, R., … Moser, T. (2021). RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.0586-21.2021 chicago: Butola, Tanvi, Theocharis Alvanos, Anika Hintze, Peter Koppensteiner, David Kleindienst, Ryuichi Shigemoto, Carolin Wichmann, and Tobias Moser. “RIM-Binding Protein 2 Organizes Ca21 Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” Journal of Neuroscience. Society for Neuroscience, 2021. https://doi.org/10.1523/JNEUROSCI.0586-21.2021. ieee: T. Butola et al., “RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse,” Journal of Neuroscience, vol. 41, no. 37. Society for Neuroscience, pp. 7742–7767, 2021. ista: Butola T, Alvanos T, Hintze A, Koppensteiner P, Kleindienst D, Shigemoto R, Wichmann C, Moser T. 2021. RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 41(37), 7742–7767. mla: Butola, Tanvi, et al. “RIM-Binding Protein 2 Organizes Ca21 Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” Journal of Neuroscience, vol. 41, no. 37, Society for Neuroscience, 2021, pp. 7742–67, doi:10.1523/JNEUROSCI.0586-21.2021. short: T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto, C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767. date_created: 2021-09-27T14:33:13Z date_published: 2021-09-15T00:00:00Z date_updated: 2023-08-14T06:56:30Z day: '15' ddc: - '570' department: - _id: RySh doi: 10.1523/JNEUROSCI.0586-21.2021 external_id: isi: - '000752287700005' pmid: - '34353898' file: - access_level: open_access checksum: 769ab627c7355a50ccfd445e43a5f351 content_type: application/pdf creator: dernst date_created: 2022-05-31T09:10:15Z date_updated: 2022-05-31T09:10:15Z file_id: '11423' file_name: 2021_JourNeuroscience_Butola.pdf file_size: 11571961 relation: main_file success: 1 file_date_updated: 2022-05-31T09:10:15Z has_accepted_license: '1' intvolume: ' 41' isi: 1 issue: '37' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: 7742-7767 pmid: 1 publication: Journal of Neuroscience publication_identifier: eissn: - 1529-2401 issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience quality_controlled: '1' scopus_import: '1' status: public title: RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 41 year: '2021' ... --- _id: '10403' abstract: - lang: eng text: Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits. acknowledgement: This study was supported by the Centre National de la Recherche Scientifique and the Agence Nationale de la Recherche (ANR-13-BSV4-00166, to LC and DAD). TA was supported by fellowships from the Fondation pour la Recherche Medicale and the Swedish Research Council. We thank Dmitry Ershov from the Image Analysis Hub of the Institut Pasteur, Elodie Le Monnier, Elena Hollergschwandtner, Vanessa Zheden, and Corinne Nantet for technical support and Haining Zhong for providing the Venus-tagged PSD95 mouse line. We would like to thank Alberto Bacci, Ann Lohof, and Nelson Rebola for comments on the manuscript. article_number: e65954 article_processing_charge: No article_type: original author: - first_name: Celia full_name: Biane, Celia last_name: Biane - first_name: Florian full_name: Rückerl, Florian last_name: Rückerl - first_name: Therese full_name: Abrahamsson, Therese last_name: Abrahamsson - first_name: Cécile full_name: Saint-Cloment, Cécile last_name: Saint-Cloment - first_name: Jean full_name: Mariani, Jean last_name: Mariani - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: David A. full_name: Digregorio, David A. last_name: Digregorio - first_name: Rachel M. full_name: Sherrard, Rachel M. last_name: Sherrard - first_name: Laurence full_name: Cathala, Laurence last_name: Cathala citation: ama: Biane C, Rückerl F, Abrahamsson T, et al. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. eLife. 2021;10. doi:10.7554/eLife.65954 apa: Biane, C., Rückerl, F., Abrahamsson, T., Saint-Cloment, C., Mariani, J., Shigemoto, R., … Cathala, L. (2021). Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.65954 chicago: Biane, Celia, Florian Rückerl, Therese Abrahamsson, Cécile Saint-Cloment, Jean Mariani, Ryuichi Shigemoto, David A. Digregorio, Rachel M. Sherrard, and Laurence Cathala. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/eLife.65954. ieee: C. Biane et al., “Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons,” eLife, vol. 10. eLife Sciences Publications, 2021. ista: Biane C, Rückerl F, Abrahamsson T, Saint-Cloment C, Mariani J, Shigemoto R, Digregorio DA, Sherrard RM, Cathala L. 2021. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. eLife. 10, e65954. mla: Biane, Celia, et al. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” ELife, vol. 10, e65954, eLife Sciences Publications, 2021, doi:10.7554/eLife.65954. short: C. Biane, F. Rückerl, T. Abrahamsson, C. Saint-Cloment, J. Mariani, R. Shigemoto, D.A. Digregorio, R.M. Sherrard, L. Cathala, ELife 10 (2021). date_created: 2021-12-05T23:01:40Z date_published: 2021-11-03T00:00:00Z date_updated: 2023-08-14T13:12:07Z day: '03' ddc: - '570' department: - _id: RySh doi: 10.7554/eLife.65954 external_id: isi: - '000715789500001' file: - access_level: open_access checksum: c7c33c3319428d56e332e22349c50ed3 content_type: application/pdf creator: cchlebak date_created: 2021-12-10T08:31:41Z date_updated: 2021-12-10T08:31:41Z file_id: '10528' file_name: 2021_eLife_Biane.pdf file_size: 13131322 relation: main_file success: 1 file_date_updated: 2021-12-10T08:31:41Z has_accepted_license: '1' intvolume: ' 10' isi: 1 language: - iso: eng month: '11' oa: 1 oa_version: Published Version publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 10 year: '2021' ... --- _id: '9437' abstract: - lang: eng text: The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation. acknowledgement: We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik. article_number: e68274 article_processing_charge: No article_type: original author: - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: David H full_name: Vandael, David H id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87 last_name: Vandael orcid: 0000-0001-7577-1676 - first_name: Diego full_name: Fernández-Fernández, Diego last_name: Fernández-Fernández - first_name: Thorsten full_name: Fritzius, Thorsten last_name: Fritzius - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Hüseyin C full_name: Önal, Hüseyin C id: 4659D740-F248-11E8-B48F-1D18A9856A87 last_name: Önal orcid: 0000-0002-2771-2011 - first_name: Jacqueline-Claire full_name: Montanaro-Punzengruber, Jacqueline-Claire id: 3786AB44-F248-11E8-B48F-1D18A9856A87 last_name: Montanaro-Punzengruber - first_name: Martin full_name: Gassmann, Martin last_name: Gassmann - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Akos full_name: Kulik, Akos last_name: Kulik - first_name: Bernhard full_name: Bettler, Bernhard last_name: Bettler - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 citation: ama: Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 2021;10. doi:10.7554/ELIFE.68274 apa: Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. ELife. eLife Sciences Publications. https://doi.org/10.7554/ELIFE.68274 chicago: Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/ELIFE.68274. ieee: P. Bhandari et al., “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” eLife, vol. 10. eLife Sciences Publications, 2021. ista: Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal HC, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B, Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274. mla: Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” ELife, vol. 10, e68274, eLife Sciences Publications, 2021, doi:10.7554/ELIFE.68274. short: P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, H.C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021). date_created: 2021-05-30T22:01:23Z date_published: 2021-04-29T00:00:00Z date_updated: 2024-03-27T23:30:30Z day: '29' ddc: - '570' department: - _id: RySh - _id: PeJo doi: 10.7554/ELIFE.68274 ec_funded: 1 external_id: isi: - '000651761700001' file: - access_level: open_access checksum: 6ebcb79999f889766f7cd79ee134ad28 content_type: application/pdf creator: cziletti date_created: 2021-05-31T09:43:09Z date_updated: 2021-05-31T09:43:09Z file_id: '9440' file_name: 2021_eLife_Bhandari.pdf file_size: 8174719 relation: main_file success: 1 file_date_updated: 2021-05-31T09:43:09Z has_accepted_license: '1' intvolume: ' 10' isi: 1 language: - iso: eng month: '04' oa: 1 oa_version: Published Version project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: link: - relation: earlier_version url: https://doi.org/10.1101/2020.04.16.045112 record: - id: '9562' relation: dissertation_contains status: public scopus_import: '1' status: public title: GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 10 year: '2021' ... --- _id: '9562' abstract: - lang: eng text: Left-right asymmetries can be considered a fundamental organizational principle of the vertebrate central nervous system. The hippocampal CA3-CA1 pyramidal cell synaptic connection shows an input-side dependent asymmetry where the hemispheric location of the presynaptic CA3 neuron determines the synaptic properties. Left-input synapses terminating on apical dendrites in stratum radiatum have a higher density of NMDA receptor subunit GluN2B, a lower density of AMPA receptor subunit GluA1 and smaller areas with less often perforated PSDs. On the other hand, left-input synapses terminating on basal dendrites in stratum oriens have lower GluN2B densities than right-input ones. Apical and basal synapses further employ different signaling pathways involved in LTP. SDS-digested freeze-fracture replica labeling can visualize synaptic membrane proteins with high sensitivity and resolution, and has been used to reveal the asymmetry at the electron microscopic level. However, it requires time-consuming manual demarcation of the synaptic surface for quantitative measurements. To facilitate the analysis of replica labeling, I first developed a software named Darea, which utilizes deep-learning to automatize this demarcation. With Darea I characterized the synaptic distribution of NMDA and AMPA receptors as well as the voltage-gated Ca2+ channels in CA1 stratum radiatum and oriens. Second, I explored the role of GluN2B and its carboxy-terminus in the establishment of input-side dependent hippocampal asymmetry. In conditional knock-out mice lacking GluN2B expression in CA1 and GluN2B-2A swap mice, where GluN2B carboxy-terminus was exchanged to that of GluN2A, no significant asymmetries of GluN2B, GluA1 and PSD area were detected. We further discovered a previously unknown functional asymmetry of GluN2A, which was also lost in the swap mouse. These results demonstrate that GluN2B carboxy-terminus plays a critical role in normal formation of input-side dependent asymmetry. acknowledged_ssus: - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst citation: ama: 'Kleindienst D. 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning. 2021. doi:10.15479/at:ista:9562' apa: 'Kleindienst, D. (2021). 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:9562' chicago: 'Kleindienst, David. “2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:9562.' ieee: 'D. Kleindienst, “2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning,” Institute of Science and Technology Austria, 2021.' ista: 'Kleindienst D. 2021. 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning. Institute of Science and Technology Austria.' mla: 'Kleindienst, David. 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:9562.' short: 'D. Kleindienst, 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning, Institute of Science and Technology Austria, 2021.' date_created: 2021-06-17T14:10:47Z date_published: 2021-06-01T00:00:00Z date_updated: 2023-09-11T12:55:53Z day: '01' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: RySh doi: 10.15479/at:ista:9562 file: - access_level: open_access checksum: 659df5518db495f679cb1df9e9bd1d94 content_type: application/pdf creator: dkleindienst date_created: 2021-06-17T14:03:14Z date_updated: 2022-07-02T22:30:04Z embargo: 2022-07-01 file_id: '9563' file_name: Thesis.pdf file_size: 77299142 relation: main_file - access_level: closed checksum: 3bcf63a2b19e5b6663be051bea332748 content_type: application/zip creator: dkleindienst date_created: 2021-06-17T14:04:30Z date_updated: 2022-07-02T22:30:04Z embargo_to: open_access file_id: '9564' file_name: Thesis_source.zip file_size: 369804895 relation: source_file file_date_updated: 2022-07-02T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '124' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '9756' relation: part_of_dissertation status: public - id: '9437' relation: part_of_dissertation status: public - id: '8532' relation: part_of_dissertation status: public - id: '612' relation: part_of_dissertation status: public status: public supervisor: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 title: '2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning' type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2021' ... --- _id: '9756' abstract: - lang: eng text: High-resolution visualization and quantification of membrane proteins contribute to the understanding of their functions and the roles they play in physiological and pathological conditions. Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL) is a powerful electron microscopy method to study quantitatively the two-dimensional distribution of transmembrane proteins and their tightly associated proteins. During treatment with SDS, intracellular organelles and proteins not anchored to the replica are dissolved, whereas integral membrane proteins captured and stabilized by carbon/platinum deposition remain on the replica. Their intra- and extracellular domains become exposed on the surface of the replica, facilitating the accessibility of antibodies and, therefore, providing higher labeling efficiency than those obtained with other immunoelectron microscopy techniques. In this chapter, we describe the protocols of SDS-FRL adapted for mammalian brain samples, and optimization of the SDS treatment to increase the labeling efficiency for quantification of Cav2.1, the alpha subunit of P/Q-type voltage-dependent calcium channels utilizing deep learning algorithms. acknowledgement: This work was supported by the European Union (European Research Council Advanced grant no. 694539 and Human Brain Project Ref. 720270 to R. S.) and the Austrian Academy of Sciences (DOC fellowship to D.K.). alternative_title: - Neuromethods article_processing_charge: No author: - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Harumi full_name: Harada, Harumi id: 2E55CDF2-F248-11E8-B48F-1D18A9856A87 last_name: Harada orcid: 0000-0001-7429-7896 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: 'Kaufmann W, Kleindienst D, Harada H, Shigemoto R. High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL). In: Receptor and Ion Channel Detection in the Brain. Vol 169. Neuromethods. New York: Humana; 2021:267-283. doi:10.1007/978-1-0716-1522-5_19' apa: 'Kaufmann, W., Kleindienst, D., Harada, H., & Shigemoto, R. (2021). High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL). In Receptor and Ion Channel Detection in the Brain (Vol. 169, pp. 267–283). New York: Humana. https://doi.org/10.1007/978-1-0716-1522-5_19' chicago: 'Kaufmann, Walter, David Kleindienst, Harumi Harada, and Ryuichi Shigemoto. “High-Resolution Localization and Quantitation of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL).” In Receptor and Ion Channel Detection in the Brain, 169:267–83. Neuromethods. New York: Humana, 2021. https://doi.org/10.1007/978-1-0716-1522-5_19.' ieee: 'W. Kaufmann, D. Kleindienst, H. Harada, and R. Shigemoto, “High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL),” in Receptor and Ion Channel Detection in the Brain, vol. 169, New York: Humana, 2021, pp. 267–283.' ista: 'Kaufmann W, Kleindienst D, Harada H, Shigemoto R. 2021.High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL). In: Receptor and Ion Channel Detection in the Brain. Neuromethods, vol. 169, 267–283.' mla: Kaufmann, Walter, et al. “High-Resolution Localization and Quantitation of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL).” Receptor and Ion Channel Detection in the Brain, vol. 169, Humana, 2021, pp. 267–83, doi:10.1007/978-1-0716-1522-5_19. short: W. Kaufmann, D. Kleindienst, H. Harada, R. Shigemoto, in:, Receptor and Ion Channel Detection in the Brain, Humana, New York, 2021, pp. 267–283. date_created: 2021-07-30T09:34:56Z date_published: 2021-07-27T00:00:00Z date_updated: 2024-03-27T23:30:30Z day: '27' ddc: - '573' department: - _id: RySh - _id: EM-Fac doi: 10.1007/978-1-0716-1522-5_19 ec_funded: 1 has_accepted_license: '1' intvolume: ' 169' keyword: - 'Freeze-fracture replica: Deep learning' - Immunogold labeling - Integral membrane protein - Electron microscopy language: - iso: eng month: '07' oa_version: None page: 267-283 place: New York project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 25CBA828-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '720270' name: Human Brain Project Specific Grant Agreement 1 (HBP SGA 1) publication: ' Receptor and Ion Channel Detection in the Brain' publication_identifier: eisbn: - '9781071615225' isbn: - '9781071615218' publication_status: published publisher: Humana quality_controlled: '1' related_material: record: - id: '9562' relation: dissertation_contains status: public series_title: Neuromethods status: public title: High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL) type: book_chapter user_id: D865714E-FA4E-11E9-B85B-F5C5E5697425 volume: 169 year: '2021' ... --- _id: '7148' abstract: - lang: eng text: In the cerebellum, GluD2 is exclusively expressed in Purkinje cells, where it regulates synapse formation and regeneration, synaptic plasticity, and motor learning. Delayed cognitive development in humans with GluD2 gene mutations suggests extracerebellar functions of GluD2. However, extracerebellar expression of GluD2 and its relationship with that of GluD1 are poorly understood. GluD2 mRNA and protein were widely detected, with relatively high levels observed in the olfactory glomerular layer, medial prefrontal cortex, cingulate cortex, retrosplenial granular cortex, olfactory tubercle, subiculum, striatum, lateral septum, anterodorsal thalamic nucleus, and arcuate hypothalamic nucleus. These regions were also enriched for GluD1, and many individual neurons coexpressed the two GluDs. In the retrosplenial granular cortex, GluD1 and GluD2 were selectively expressed at PSD‐95‐expressing glutamatergic synapses, and their coexpression on the same synapses was shown by SDS‐digested freeze‐fracture replica labeling. Biochemically, GluD1 and GluD2 formed coimmunoprecipitable complex formation in HEK293T cells and in the cerebral cortex and hippocampus. We further estimated the relative protein amount by quantitative immunoblotting using GluA2/GluD2 and GluA2/GluD1 chimeric proteins as standards for titration of GluD1 and GluD2 antibodies. Intriguingly, the relative amount of GluD2 was almost comparable to that of GluD1 in the postsynaptic density fraction prepared from the cerebral cortex and hippocampus. In contrast, GluD2 was overwhelmingly predominant in the cerebellum. Thus, we have determined the relative extracerebellar expression of GluD1 and GluD2 at regional, neuronal, and synaptic levels. These data provide a molecular–anatomical basis for possible competitive and cooperative interactions of GluD family members at synapses in various brain regions. acknowledgement: This study was supported by Grants-in-Aid for Scientific Research to K.K. (18K06813), Y.M. (17K08503, 17H0631319), and K.S. (16H04650) and a grant for Scientific Research on Innovative Areas to K.S (16H06276) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). We thank K. Akashi, I. Watanabe-Iida, Y. Suzuki, and H. Azechi for technical assistance and advice, and H. Uchida for valuable discussions. We thank E. Kushiya,I. Yabe, C. Ohori, Y. Mochizuki, Y. Ishikawa, and N. Ishimoto for technical assistance in generating GluD1-KO mice. article_processing_charge: No article_type: original author: - first_name: Chihiro full_name: Nakamoto, Chihiro last_name: Nakamoto - first_name: Kohtarou full_name: Konno, Kohtarou last_name: Konno - first_name: Taisuke full_name: Miyazaki, Taisuke last_name: Miyazaki - first_name: Ena full_name: Nakatsukasa, Ena last_name: Nakatsukasa - first_name: Rie full_name: Natsume, Rie last_name: Natsume - first_name: Manabu full_name: Abe, Manabu last_name: Abe - first_name: Meiko full_name: Kawamura, Meiko last_name: Kawamura - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Miwako full_name: Yamasaki, Miwako last_name: Yamasaki - first_name: Kenji full_name: Sakimura, Kenji last_name: Sakimura - first_name: Masahiko full_name: Watanabe, Masahiko last_name: Watanabe citation: ama: Nakamoto C, Konno K, Miyazaki T, et al. Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. Journal of Comparative Neurology. 2020;528(6):1003-1027. doi:10.1002/cne.24792 apa: Nakamoto, C., Konno, K., Miyazaki, T., Nakatsukasa, E., Natsume, R., Abe, M., … Watanabe, M. (2020). Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. Journal of Comparative Neurology. Wiley. https://doi.org/10.1002/cne.24792 chicago: Nakamoto, Chihiro, Kohtarou Konno, Taisuke Miyazaki, Ena Nakatsukasa, Rie Natsume, Manabu Abe, Meiko Kawamura, et al. “Expression Mapping, Quantification, and Complex Formation of GluD1 and GluD2 Glutamate Receptors in Adult Mouse Brain.” Journal of Comparative Neurology. Wiley, 2020. https://doi.org/10.1002/cne.24792. ieee: C. Nakamoto et al., “Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain,” Journal of Comparative Neurology, vol. 528, no. 6. Wiley, pp. 1003–1027, 2020. ista: Nakamoto C, Konno K, Miyazaki T, Nakatsukasa E, Natsume R, Abe M, Kawamura M, Fukazawa Y, Shigemoto R, Yamasaki M, Sakimura K, Watanabe M. 2020. Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. Journal of Comparative Neurology. 528(6), 1003–1027. mla: Nakamoto, Chihiro, et al. “Expression Mapping, Quantification, and Complex Formation of GluD1 and GluD2 Glutamate Receptors in Adult Mouse Brain.” Journal of Comparative Neurology, vol. 528, no. 6, Wiley, 2020, pp. 1003–27, doi:10.1002/cne.24792. short: C. Nakamoto, K. Konno, T. Miyazaki, E. Nakatsukasa, R. Natsume, M. Abe, M. Kawamura, Y. Fukazawa, R. Shigemoto, M. Yamasaki, K. Sakimura, M. Watanabe, Journal of Comparative Neurology 528 (2020) 1003–1027. date_created: 2019-12-04T16:09:29Z date_published: 2020-04-01T00:00:00Z date_updated: 2023-08-17T14:06:50Z day: '01' ddc: - '571' - '599' department: - _id: RySh doi: 10.1002/cne.24792 external_id: isi: - '000496410200001' pmid: - '31625608' has_accepted_license: '1' intvolume: ' 528' isi: 1 issue: '6' language: - iso: eng month: '04' oa_version: None page: 1003-1027 pmid: 1 publication: Journal of Comparative Neurology publication_identifier: eissn: - 1096-9861 issn: - 0021-9967 publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 528 year: '2020' ... --- _id: '7339' abstract: - lang: eng text: Cytoskeletal filaments such as microtubules (MTs) and filamentous actin (F-actin) dynamically support cell structure and functions. In central presynaptic terminals, F-actin is expressed along the release edge and reportedly plays diverse functional roles, but whether axonal MTs extend deep into terminals and play any physiological role remains controversial. At the calyx of Held in rats of either sex, confocal and high-resolution microscopy revealed that MTs enter deep into presynaptic terminal swellings and partially colocalize with a subset of synaptic vesicles (SVs). Electrophysiological analysis demonstrated that depolymerization of MTs specifically prolonged the slow-recovery time component of EPSCs from short-term depression induced by a train of high-frequency stimulation, whereas depolymerization of F-actin specifically prolonged the fast-recovery component. In simultaneous presynaptic and postsynaptic action potential recordings, depolymerization of MTs or F-actin significantly impaired the fidelity of high-frequency neurotransmission. We conclude that MTs and F-actin differentially contribute to slow and fast SV replenishment, thereby maintaining high-frequency neurotransmission. article_processing_charge: No article_type: original author: - first_name: Lashmi full_name: Piriya Ananda Babu, Lashmi last_name: Piriya Ananda Babu - first_name: Han Ying full_name: Wang, Han Ying last_name: Wang - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Laurent full_name: Guillaud, Laurent last_name: Guillaud - first_name: Tomoyuki full_name: Takahashi, Tomoyuki last_name: Takahashi citation: ama: Piriya Ananda Babu L, Wang HY, Eguchi K, Guillaud L, Takahashi T. Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission. Journal of neuroscience. 2020;40(1):131-142. doi:10.1523/JNEUROSCI.1571-19.2019 apa: Piriya Ananda Babu, L., Wang, H. Y., Eguchi, K., Guillaud, L., & Takahashi, T. (2020). Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1571-19.2019 chicago: Piriya Ananda Babu, Lashmi, Han Ying Wang, Kohgaku Eguchi, Laurent Guillaud, and Tomoyuki Takahashi. “Microtubule and Actin Differentially Regulate Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission.” Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/JNEUROSCI.1571-19.2019. ieee: L. Piriya Ananda Babu, H. Y. Wang, K. Eguchi, L. Guillaud, and T. Takahashi, “Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission,” Journal of neuroscience, vol. 40, no. 1. Society for Neuroscience, pp. 131–142, 2020. ista: Piriya Ananda Babu L, Wang HY, Eguchi K, Guillaud L, Takahashi T. 2020. Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission. Journal of neuroscience. 40(1), 131–142. mla: Piriya Ananda Babu, Lashmi, et al. “Microtubule and Actin Differentially Regulate Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission.” Journal of Neuroscience, vol. 40, no. 1, Society for Neuroscience, 2020, pp. 131–42, doi:10.1523/JNEUROSCI.1571-19.2019. short: L. Piriya Ananda Babu, H.Y. Wang, K. Eguchi, L. Guillaud, T. Takahashi, Journal of Neuroscience 40 (2020) 131–142. date_created: 2020-01-19T23:00:38Z date_published: 2020-01-02T00:00:00Z date_updated: 2023-08-17T14:25:23Z day: '02' ddc: - '570' department: - _id: RySh doi: 10.1523/JNEUROSCI.1571-19.2019 external_id: isi: - '000505167600013' pmid: - '31767677' file: - access_level: open_access checksum: 92f5e8a47f454fc131fb94cd7f106e60 content_type: application/pdf creator: dernst date_created: 2020-01-20T14:44:10Z date_updated: 2020-07-14T12:47:56Z file_id: '7345' file_name: 2020_JourNeuroscience_Piriya.pdf file_size: 4460781 relation: main_file file_date_updated: 2020-07-14T12:47:56Z has_accepted_license: '1' intvolume: ' 40' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 131-142 pmid: 1 publication: Journal of neuroscience publication_identifier: eissn: - '15292401' publication_status: published publisher: Society for Neuroscience quality_controlled: '1' scopus_import: '1' status: public title: Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 40 year: '2020' ... --- _id: '7664' abstract: - lang: eng text: Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control of network activity and information processing in hippocampal circuits by regulating neuronal excitability and synaptic transmission. The dysfunction in the dentate gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the involvement of GABAB receptors in AD, to determine their subcellular localisation and possible alteration in granule cells of the DG in a mouse model of AD at 12 months of age, we used high-resolution immunoelectron microscopic analysis. Immunohistochemistry at the light microscopic level showed that the regional and cellular expression pattern of GABAB1 was similar in an AD model mouse expressing mutated human amyloid precursor protein and presenilin1 (APP/PS1) and in age-matched wild type mice. High-resolution immunoelectron microscopy revealed a distance-dependent gradient of immunolabelling for GABAB receptors, increasing from proximal to distal dendrites in both wild type and APP/PS1 mice. However, the overall density of GABAB receptors at the neuronal surface of these postsynaptic compartments of granule cells was significantly reduced in APP/PS1 mice. Parallel to this reduction in surface receptors, we found a significant increase in GABAB1 at cytoplasmic sites. GABAB receptors were also detected at presynaptic sites in the molecular layer of the DG. We also found a decrease in plasma membrane GABAB receptors in axon terminals contacting dendritic spines of granule cells, which was more pronounced in the outer than in the inner molecular layer. Altogether, our data showing post- and presynaptic reduction in surface GABAB receptors in the DG suggest the alteration of the GABAB-mediated modulation of excitability and synaptic transmission in granule cells, which may contribute to the cognitive dysfunctions in the APP/PS1 model of AD article_number: '2459' article_processing_charge: No article_type: original author: - first_name: Alejandro full_name: Martín-Belmonte, Alejandro last_name: Martín-Belmonte - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Rocío full_name: Alfaro-Ruíz, Rocío last_name: Alfaro-Ruíz - first_name: Ana Esther full_name: Moreno-Martínez, Ana Esther last_name: Moreno-Martínez - first_name: Luis full_name: De La Ossa, Luis last_name: De La Ossa - first_name: José full_name: Martínez-Hernández, José last_name: Martínez-Hernández - first_name: Alain full_name: Buisson, Alain last_name: Buisson - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Rafael full_name: Luján, Rafael last_name: Luján citation: ama: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International journal of molecular sciences. 2020;21(7). doi:10.3390/ijms21072459 apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21072459 chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, Ryuichi Shigemoto, Yugo Fukazawa, and Rafael Luján. “Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21072459. ieee: A. Martín-Belmonte et al., “Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease,” International journal of molecular sciences, vol. 21, no. 7. MDPI, 2020. ista: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa L, Martínez-Hernández J, Buisson A, Shigemoto R, Fukazawa Y, Luján R. 2020. Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International journal of molecular sciences. 21(7), 2459. mla: Martín-Belmonte, Alejandro, et al. “Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” International Journal of Molecular Sciences, vol. 21, no. 7, 2459, MDPI, 2020, doi:10.3390/ijms21072459. short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De La Ossa, J. Martínez-Hernández, A. Buisson, R. Shigemoto, Y. Fukazawa, R. Luján, International Journal of Molecular Sciences 21 (2020). date_created: 2020-04-19T22:00:55Z date_published: 2020-04-02T00:00:00Z date_updated: 2023-08-21T06:13:19Z day: '02' ddc: - '570' department: - _id: RySh doi: 10.3390/ijms21072459 external_id: isi: - '000535574200201' pmid: - '32252271' file: - access_level: open_access checksum: b9d2f1657d8c4a74b01a62b474d009b0 content_type: application/pdf creator: dernst date_created: 2020-04-20T11:43:18Z date_updated: 2020-07-14T12:48:01Z file_id: '7669' file_name: 2020_JournMolecSciences_Martin_Belmonte.pdf file_size: 2941197 relation: main_file file_date_updated: 2020-07-14T12:48:01Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '7' language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 publication: International journal of molecular sciences publication_identifier: eissn: - '14220067' publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer's disease tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 21 year: '2020' ... --- _id: '7665' abstract: - lang: eng text: Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability. Furthermore, preparation at PT allows electrophysiological recording immediately after slicing resulting in higher detectability of long-term depression (LTD) after motor learning compared with that at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions. article_number: '63' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Elena full_name: Hollergschwandtner, Elena id: 3C054040-F248-11E8-B48F-1D18A9856A87 last_name: Hollergschwandtner - first_name: Makoto full_name: Itakura, Makoto last_name: Itakura - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Eguchi K, Velicky P, Saeckl E, et al. Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. 2020;14. doi:10.3389/fncel.2020.00063 apa: Eguchi, K., Velicky, P., Saeckl, E., Itakura, M., Fukazawa, Y., Danzl, J. G., & Shigemoto, R. (2020). Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. Frontiers Media. https://doi.org/10.3389/fncel.2020.00063 chicago: Eguchi, Kohgaku, Philipp Velicky, Elena Saeckl, Makoto Itakura, Yugo Fukazawa, Johann G Danzl, and Ryuichi Shigemoto. “Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions.” Frontiers in Cellular Neuroscience. Frontiers Media, 2020. https://doi.org/10.3389/fncel.2020.00063. ieee: K. Eguchi et al., “Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions,” Frontiers in Cellular Neuroscience, vol. 14. Frontiers Media, 2020. ista: Eguchi K, Velicky P, Saeckl E, Itakura M, Fukazawa Y, Danzl JG, Shigemoto R. 2020. Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. 14, 63. mla: Eguchi, Kohgaku, et al. “Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions.” Frontiers in Cellular Neuroscience, vol. 14, 63, Frontiers Media, 2020, doi:10.3389/fncel.2020.00063. short: K. Eguchi, P. Velicky, E. Saeckl, M. Itakura, Y. Fukazawa, J.G. Danzl, R. Shigemoto, Frontiers in Cellular Neuroscience 14 (2020). date_created: 2020-04-19T22:00:55Z date_published: 2020-03-19T00:00:00Z date_updated: 2023-08-21T06:12:48Z day: '19' ddc: - '570' department: - _id: JoDa - _id: RySh doi: 10.3389/fncel.2020.00063 ec_funded: 1 external_id: isi: - '000525582200001' file: - access_level: open_access checksum: 1c145123c6f8dc3e2e4bd5a66a1ad60e content_type: application/pdf creator: dernst date_created: 2020-04-20T10:59:49Z date_updated: 2020-07-14T12:48:01Z file_id: '7668' file_name: 2020_FrontiersCellularNeurosc_Eguchi.pdf file_size: 9227283 relation: main_file file_date_updated: 2020-07-14T12:48:01Z has_accepted_license: '1' intvolume: ' 14' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version project: - _id: 2659CC84-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '793482' name: 'Ultrastructural analysis of phosphoinositides in nerve terminals: distribution, dynamics and physiological roles in synaptic transmission' - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: B67AFEDC-15C9-11EA-A837-991A96BB2854 name: IST Austria Open Access Fund publication: Frontiers in Cellular Neuroscience publication_identifier: issn: - '16625102' publication_status: published publisher: Frontiers Media quality_controlled: '1' scopus_import: '1' status: public title: Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 14 year: '2020' ... --- _id: '7878' abstract: - lang: eng text: Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions. article_number: e56839 article_processing_charge: No article_type: original author: - first_name: Jin full_name: Bao, Jin last_name: Bao - first_name: Michael full_name: Graupner, Michael last_name: Graupner - first_name: Guadalupe full_name: Astorga, Guadalupe last_name: Astorga - first_name: Thibault full_name: Collin, Thibault last_name: Collin - first_name: Abdelali full_name: Jalil, Abdelali last_name: Jalil - first_name: Dwi Wahyu full_name: Indriati, Dwi Wahyu last_name: Indriati - first_name: Jonathan full_name: Bradley, Jonathan last_name: Bradley - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Isabel full_name: Llano, Isabel last_name: Llano citation: ama: Bao J, Graupner M, Astorga G, et al. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife. 2020;9. doi:10.7554/eLife.56839 apa: Bao, J., Graupner, M., Astorga, G., Collin, T., Jalil, A., Indriati, D. W., … Llano, I. (2020). Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.56839 chicago: Bao, Jin, Michael Graupner, Guadalupe Astorga, Thibault Collin, Abdelali Jalil, Dwi Wahyu Indriati, Jonathan Bradley, Ryuichi Shigemoto, and Isabel Llano. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.56839. ieee: J. Bao et al., “Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Bao J, Graupner M, Astorga G, Collin T, Jalil A, Indriati DW, Bradley J, Shigemoto R, Llano I. 2020. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife. 9, e56839. mla: Bao, Jin, et al. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” ELife, vol. 9, e56839, eLife Sciences Publications, 2020, doi:10.7554/eLife.56839. short: J. Bao, M. Graupner, G. Astorga, T. Collin, A. Jalil, D.W. Indriati, J. Bradley, R. Shigemoto, I. Llano, ELife 9 (2020). date_created: 2020-05-24T22:00:58Z date_published: 2020-05-13T00:00:00Z date_updated: 2023-08-21T06:26:50Z day: '13' ddc: - '570' department: - _id: RySh doi: 10.7554/eLife.56839 external_id: isi: - '000535191600001' pmid: - '32401196' file: - access_level: open_access checksum: 8ea99bb6660cc407dbdb00c173b01683 content_type: application/pdf creator: dernst date_created: 2020-05-26T09:34:54Z date_updated: 2020-07-14T12:48:04Z file_id: '7891' file_name: 2020_eLife_Bao.pdf file_size: 4832050 relation: main_file file_date_updated: 2020-07-14T12:48:04Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: eissn: - 2050084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 9 year: '2020' ... --- _id: '7908' abstract: - lang: eng text: Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses. article_processing_charge: No article_type: original author: - first_name: Han Ying full_name: Wang, Han Ying last_name: Wang - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Takayuki full_name: Yamashita, Takayuki last_name: Yamashita - first_name: Tomoyuki full_name: Takahashi, Tomoyuki last_name: Takahashi citation: ama: Wang HY, Eguchi K, Yamashita T, Takahashi T. Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. Journal of Neuroscience. 2020;40(21):4103-4115. doi:10.1523/JNEUROSCI.2946-19.2020 apa: Wang, H. Y., Eguchi, K., Yamashita, T., & Takahashi, T. (2020). Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.2946-19.2020 chicago: Wang, Han Ying, Kohgaku Eguchi, Takayuki Yamashita, and Tomoyuki Takahashi. “Frequency-Dependent Block of Excitatory Neurotransmission by Isoflurane via Dual Presynaptic Mechanisms.” Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/JNEUROSCI.2946-19.2020. ieee: H. Y. Wang, K. Eguchi, T. Yamashita, and T. Takahashi, “Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms,” Journal of Neuroscience, vol. 40, no. 21. Society for Neuroscience, pp. 4103–4115, 2020. ista: Wang HY, Eguchi K, Yamashita T, Takahashi T. 2020. Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. Journal of Neuroscience. 40(21), 4103–4115. mla: Wang, Han Ying, et al. “Frequency-Dependent Block of Excitatory Neurotransmission by Isoflurane via Dual Presynaptic Mechanisms.” Journal of Neuroscience, vol. 40, no. 21, Society for Neuroscience, 2020, pp. 4103–15, doi:10.1523/JNEUROSCI.2946-19.2020. short: H.Y. Wang, K. Eguchi, T. Yamashita, T. Takahashi, Journal of Neuroscience 40 (2020) 4103–4115. date_created: 2020-05-31T22:00:48Z date_published: 2020-05-20T00:00:00Z date_updated: 2023-08-21T06:31:25Z day: '20' ddc: - '570' department: - _id: RySh doi: 10.1523/JNEUROSCI.2946-19.2020 external_id: isi: - '000535694700004' file: - access_level: open_access checksum: 6571607ea9036154b67cc78e848a7f7d content_type: application/pdf creator: dernst date_created: 2020-06-02T09:12:16Z date_updated: 2020-07-14T12:48:05Z file_id: '7912' file_name: 2020_JourNeuroscience_Wang.pdf file_size: 3817360 relation: main_file file_date_updated: 2020-07-14T12:48:05Z has_accepted_license: '1' intvolume: ' 40' isi: 1 issue: '21' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 4103-4115 publication: Journal of Neuroscience publication_identifier: eissn: - '15292401' publication_status: published publisher: Society for Neuroscience quality_controlled: '1' scopus_import: '1' status: public title: Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 40 year: '2020' ... --- _id: '7207' abstract: - lang: eng text: The hippocampus plays key roles in learning and memory and is a main target of Alzheimer's disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the synaptic deficits by which AD disables the hippocampus are not yet characterized. By combining histoblots, western blots, immunohistochemistry and high‐resolution immunoelectron microscopic methods for GABAB receptors, this study provides a quantitative description of the expression and the subcellular localization of GABAB1 in the hippocampus in a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots showed that the total amount of protein and the laminar expression pattern of GABAB1 were similar in APP/PS1 mice and in age‐matched wild‐type mice. In contrast, immunoelectron microscopic techniques showed that the subcellular localization of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age, was significantly reduced in the stratum lacunosum‐moleculare of CA1 pyramidal cells at 6 months of age and significantly reduced at the membrane surface of CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1 was paralleled by a significant increase of the subunit at the intracellular sites. We further observed a decrease of membrane‐targeted GABAB receptors in axon terminals contacting CA1 pyramidal cells. Our data demonstrate compartment‐ and age‐dependent reduction of plasma membrane‐targeted GABAB receptors in the CA1 region of the hippocampus, suggesting that this decrease might be enough to alter the GABAB‐mediated synaptic transmission taking place in AD. article_processing_charge: No article_type: original author: - first_name: Alejandro full_name: Martín-Belmonte, Alejandro last_name: Martín-Belmonte - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Rocío full_name: Alfaro-Ruíz, Rocío last_name: Alfaro-Ruíz - first_name: Ana Esther full_name: Moreno-Martínez, Ana Esther last_name: Moreno-Martínez - first_name: Luis full_name: De La Ossa, Luis last_name: De La Ossa - first_name: José full_name: Martínez-Hernández, José last_name: Martínez-Hernández - first_name: Alain full_name: Buisson, Alain last_name: Buisson - first_name: Simon full_name: Früh, Simon last_name: Früh - first_name: Bernhard full_name: Bettler, Bernhard last_name: Bettler - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Rafael full_name: Luján, Rafael last_name: Luján citation: ama: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology. 2020;30(3):554-575. doi:10.1111/bpa.12802 apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology. Wiley. https://doi.org/10.1111/bpa.12802 chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, et al. “Reduction in the Neuronal Surface of Post and Presynaptic GABA>B< Receptors in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” Brain Pathology. Wiley, 2020. https://doi.org/10.1111/bpa.12802. ieee: A. Martín-Belmonte et al., “Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer’s disease,” Brain Pathology, vol. 30, no. 3. Wiley, pp. 554–575, 2020. ista: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa L, Martínez-Hernández J, Buisson A, Früh S, Bettler B, Shigemoto R, Fukazawa Y, Luján R. 2020. Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology. 30(3), 554–575. mla: Martín-Belmonte, Alejandro, et al. “Reduction in the Neuronal Surface of Post and Presynaptic GABA>B< Receptors in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” Brain Pathology, vol. 30, no. 3, Wiley, 2020, pp. 554–75, doi:10.1111/bpa.12802. short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De La Ossa, J. Martínez-Hernández, A. Buisson, S. Früh, B. Bettler, R. Shigemoto, Y. Fukazawa, R. Luján, Brain Pathology 30 (2020) 554–575. date_created: 2019-12-22T23:00:43Z date_published: 2020-05-01T00:00:00Z date_updated: 2023-09-06T14:48:01Z day: '01' ddc: - '570' department: - _id: RySh doi: 10.1111/bpa.12802 ec_funded: 1 external_id: isi: - '000502270900001' pmid: - '31729777' file: - access_level: open_access checksum: 549cc1b18f638a21d17a939ba5563fa9 content_type: application/pdf creator: dernst date_created: 2020-09-22T09:47:19Z date_updated: 2020-09-22T09:47:19Z file_id: '8554' file_name: 2020_BrainPathology_MartinBelmonte.pdf file_size: 4220935 relation: main_file success: 1 file_date_updated: 2020-09-22T09:47:19Z has_accepted_license: '1' intvolume: ' 30' isi: 1 issue: '3' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 554-575 pmid: 1 project: - _id: 25CBA828-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '720270' name: Human Brain Project Specific Grant Agreement 1 (HBP SGA 1) - _id: 26436750-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '785907' name: Human Brain Project Specific Grant Agreement 2 (HBP SGA 2) publication: Brain Pathology publication_identifier: eissn: - '17503639' issn: - '10156305' publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer's disease tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 30 year: '2020' ... --- _id: '7525' abstract: - lang: eng text: "The medial habenula (MHb) is an evolutionary conserved epithalamic structure important for the modulation of emotional memory. It is involved in regulation of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and feeding behavior. MHb receives inputs from septal regions and projects exclusively to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project to different subnuclei of MHb: the bed nucleus of anterior commissure projects to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore, the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively. Importantly, these projections have unique features of prominent co-release of different neurotransmitters and requirement of a peculiar type of calcium channel for release. In general, synaptic neurotransmission requires an activity-dependent influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels. The calcium channel family most commonly involved in neurotransmitter release comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits, respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements. This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique mechanisms of glutamate release in this pathway. One potential example of such uniqueness is the facilitation of release by GABAB receptor (GBR) activation. Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting presynaptic calcium channels. MHb shows the highest expression levels of GBR in the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are associated with auxiliary subunits, called potassium channel tetramerization domain containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b may be involved in the unique mechanisms of neurotransmitter release mediated by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482. We next found that baclofen, a GBR agonist, has facilitatory effects on release from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed exclusively in ventral MHb may have a role in the facilitatory effects of GBR activation. In a heterologous expression system using HEK cells, we found that KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely in presynaptic active zone in IPN with KCTD12b being present only in rostral/central but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3, KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating that they may form complexes regulating vesicle release in rostral IPN. \r\nOn electrophysiological studies of wild type (WT) mice, we found that paired-pulse ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8 KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO mice, the mean variance analysis revealed significantly lower release probability in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8 and KCTD12b KO mice, and found the facilitation of release remained in both KO mice, indicating that the peculiar effects of the GBR activation in this pathway do not depend on the selective expression of these KCTD subunits in ventral MHb. However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in its termination in the absence of KCTD12b. Consistent with these functional findings, replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn summary, our study provided new insights into the physiological roles of presynaptic Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal circuit. Future studies will be required to identify the exact molecular mechanism underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals. It remains to be determined whether the prominent presence of presynaptic KCTDs at active zone could exert similar neuromodulatory functions in different pathways of the brain.\r\n" acknowledged_ssus: - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 citation: ama: Bhandari P. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. 2020. doi:10.15479/AT:ISTA:7525 apa: Bhandari, P. (2020). Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7525 chicago: Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7525. ieee: P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway,” Institute of Science and Technology Austria, 2020. ista: Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria. mla: Bhandari, Pradeep. Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7525. short: P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria, 2020. date_created: 2020-02-26T10:56:37Z date_published: 2020-02-28T00:00:00Z date_updated: 2023-09-07T13:20:03Z day: '28' ddc: - '570' degree_awarded: PhD department: - _id: RySh doi: 10.15479/AT:ISTA:7525 file: - access_level: open_access checksum: 4589234fdb12b4ad72273b311723a7b4 content_type: application/pdf creator: pbhandari date_created: 2020-02-28T08:37:53Z date_updated: 2021-03-01T23:30:04Z embargo: 2021-02-28 file_id: '7538' file_name: Pradeep Bhandari Thesis.pdf file_size: 9646346 relation: main_file title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway - access_level: closed checksum: aa79490553ca0a5c9b6fbcd152e93928 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: pbhandari date_created: 2020-02-28T08:47:14Z date_updated: 2021-03-01T23:30:04Z embargo_to: open_access file_id: '7539' file_name: Pradeep Bhandari Thesis.docx file_size: 35252164 relation: source_file title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway file_date_updated: 2021-03-01T23:30:04Z has_accepted_license: '1' keyword: - Cav2.3 - medial habenula (MHb) - interpeduncular nucleus (IPN) language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: '79' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '8532' abstract: - lang: eng text: The molecular anatomy of synapses defines their characteristics in transmission and plasticity. Precise measurements of the number and distribution of synaptic proteins are important for our understanding of synapse heterogeneity within and between brain regions. Freeze–fracture replica immunogold electron microscopy enables us to analyze them quantitatively on a two-dimensional membrane surface. Here, we introduce Darea software, which utilizes deep learning for analysis of replica images and demonstrate its usefulness for quick measurements of the pre- and postsynaptic areas, density and distribution of gold particles at synapses in a reproducible manner. We used Darea for comparing glutamate receptor and calcium channel distributions between hippocampal CA3-CA1 spine synapses on apical and basal dendrites, which differ in signaling pathways involved in synaptic plasticity. We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA) receptors with size. Interestingly, AMPA and NMDA receptors are segregated within postsynaptic sites and negatively correlated in density among both apical and basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels show similar densities in apical and basal synapses with distributions consistent with an exclusion zone model of calcium channel-release site topography. acknowledgement: "This research was funded by Austrian Academy of Sciences, DOC fellowship to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner for technical support." article_number: '6737' article_processing_charge: No article_type: original author: - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Jacqueline-Claire full_name: Montanaro-Punzengruber, Jacqueline-Claire id: 3786AB44-F248-11E8-B48F-1D18A9856A87 last_name: Montanaro-Punzengruber - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Matthew J full_name: Case, Matthew J id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87 last_name: Case - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 2020;21(18). doi:10.3390/ijms21186737 apa: Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J., Fukazawa, Y., & Shigemoto, R. (2020). Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21186737 chicago: Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari, Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21186737. ieee: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y. Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses,” International Journal of Molecular Sciences, vol. 21, no. 18. MDPI, 2020. ista: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 21(18), 6737. mla: Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” International Journal of Molecular Sciences, vol. 21, no. 18, 6737, MDPI, 2020, doi:10.3390/ijms21186737. short: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y. Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020). date_created: 2020-09-20T22:01:35Z date_published: 2020-09-14T00:00:00Z date_updated: 2024-03-27T23:30:30Z day: '14' ddc: - '570' department: - _id: RySh doi: 10.3390/ijms21186737 ec_funded: 1 external_id: isi: - '000579945300001' file: - access_level: open_access checksum: 2e4f62f3cfe945b7391fc3070e5a289f content_type: application/pdf creator: dernst date_created: 2020-09-21T14:08:58Z date_updated: 2020-09-21T14:08:58Z file_id: '8551' file_name: 2020_JournMolecSciences_Kleindienst.pdf file_size: 5748456 relation: main_file success: 1 file_date_updated: 2020-09-21T14:08:58Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '18' language: - iso: eng month: '09' oa: 1 oa_version: Published Version project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 25D32BC0-B435-11E9-9278-68D0E5697425 name: Mechanism of formation and maintenance of input side-dependent asymmetry in the hippocampus - _id: 26436750-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '785907' name: Human Brain Project Specific Grant Agreement 2 (HBP SGA 2) publication: International Journal of Molecular Sciences publication_identifier: eissn: - '14220067' issn: - '16616596' publication_status: published publisher: MDPI quality_controlled: '1' related_material: record: - id: '9562' relation: dissertation_contains status: public scopus_import: '1' status: public title: Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 21 year: '2020' ... --- _id: '6659' abstract: - lang: eng text: Chemical labeling of proteins with synthetic molecular probes offers the possibility to probe the functions of proteins of interest in living cells. However, the methods for covalently labeling targeted proteins using complementary peptide tag-probe pairs are still limited, irrespective of the versatility of such pairs in biological research. Herein, we report the new CysHis tag-Ni(II) probe pair for the specific covalent labeling of proteins. A broad-range evaluation of the reactivity profiles of the probe and the CysHis peptide tag afforded a tag-probe pair with an optimized and high labeling selectivity and reactivity. In particular, the labeling specificity of this pair was notably improved compared to the previously reported one. This pair was successfully utilized for the fluorescence imaging of membrane proteins on the surfaces of living cells, demonstrating its potential utility in biological research. acknowledgement: his work was supported by the Grant-in-Aid for Scientific Research B (JSPS KAKENHI grant no. JP17H03090 to A. O.); the Scientific Research on Innovative Areas “Chemistry for Multimolecular Crowding Biosystems” (JSPS KAKENHI grant no. JP17H06349 to A. O.); and the European Union (European Research Council Advanced grant no. 694539 and Human Brain Project Ref. 720270 to R. S.). A. O. acknowledges the financial support of the Takeda Science Foundation. article_processing_charge: No article_type: original author: - first_name: Naoki full_name: Zenmyo, Naoki last_name: Zenmyo - first_name: Hiroki full_name: Tokumaru, Hiroki last_name: Tokumaru - first_name: Shohei full_name: Uchinomiya, Shohei last_name: Uchinomiya - first_name: Hirokazu full_name: Fuchida, Hirokazu last_name: Fuchida - first_name: Shigekazu full_name: Tabata, Shigekazu id: 4427179E-F248-11E8-B48F-1D18A9856A87 last_name: Tabata - first_name: Itaru full_name: Hamachi, Itaru last_name: Hamachi - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Akio full_name: Ojida, Akio last_name: Ojida citation: ama: Zenmyo N, Tokumaru H, Uchinomiya S, et al. Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins. Bulletin of the Chemical Society of Japan. 2019;92(5):995-1000. doi:10.1246/bcsj.20190034 apa: Zenmyo, N., Tokumaru, H., Uchinomiya, S., Fuchida, H., Tabata, S., Hamachi, I., … Ojida, A. (2019). Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins. Bulletin of the Chemical Society of Japan. Bulletin of the Chemical Society of Japan. https://doi.org/10.1246/bcsj.20190034 chicago: Zenmyo, Naoki, Hiroki Tokumaru, Shohei Uchinomiya, Hirokazu Fuchida, Shigekazu Tabata, Itaru Hamachi, Ryuichi Shigemoto, and Akio Ojida. “Optimized Reaction Pair of the CysHis Tag and Ni(II)-NTA Probe for Highly Selective Chemical Labeling of Membrane Proteins.” Bulletin of the Chemical Society of Japan. Bulletin of the Chemical Society of Japan, 2019. https://doi.org/10.1246/bcsj.20190034. ieee: N. Zenmyo et al., “Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins,” Bulletin of the Chemical Society of Japan, vol. 92, no. 5. Bulletin of the Chemical Society of Japan, pp. 995–1000, 2019. ista: Zenmyo N, Tokumaru H, Uchinomiya S, Fuchida H, Tabata S, Hamachi I, Shigemoto R, Ojida A. 2019. Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins. Bulletin of the Chemical Society of Japan. 92(5), 995–1000. mla: Zenmyo, Naoki, et al. “Optimized Reaction Pair of the CysHis Tag and Ni(II)-NTA Probe for Highly Selective Chemical Labeling of Membrane Proteins.” Bulletin of the Chemical Society of Japan, vol. 92, no. 5, Bulletin of the Chemical Society of Japan, 2019, pp. 995–1000, doi:10.1246/bcsj.20190034. short: N. Zenmyo, H. Tokumaru, S. Uchinomiya, H. Fuchida, S. Tabata, I. Hamachi, R. Shigemoto, A. Ojida, Bulletin of the Chemical Society of Japan 92 (2019) 995–1000. date_created: 2019-07-21T21:59:16Z date_published: 2019-05-15T00:00:00Z date_updated: 2021-01-12T08:08:26Z day: '15' ddc: - '570' department: - _id: RySh doi: 10.1246/bcsj.20190034 ec_funded: 1 file: - access_level: open_access checksum: 186de511d6e0ca93f5d981e2443eb8cd content_type: application/pdf creator: dernst date_created: 2020-10-02T08:49:58Z date_updated: 2020-10-02T08:49:58Z file_id: '8594' file_name: 2019_BCSJ_Zenmyo.pdf file_size: 2464903 relation: main_file success: 1 file_date_updated: 2020-10-02T08:49:58Z has_accepted_license: '1' intvolume: ' 92' issue: '5' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 995-1000 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: Bulletin of the Chemical Society of Japan publication_identifier: issn: - '00092673' publication_status: published publisher: Bulletin of the Chemical Society of Japan quality_controlled: '1' scopus_import: '1' status: public title: Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 92 year: '2019' ... --- _id: '6868' abstract: - lang: eng text: "Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at the subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can be bidirectionally modulated by a HCN channel blocker, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC50 40 mM; estimated endogenous cAMP concentration 13 mM). In addition, immunogold-electron microscopy revealed HCN2 as the dominating subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2 channels control conduction velocity primarily by altering the resting membrane potential\r\nand are associated with significant metabolic costs. These results suggest that the cAMP-HCN pathway provides neuromodulators with an opportunity to finely tune energy consumption and temporal delays across axons in the brain." article_number: e42766 article_processing_charge: No article_type: original author: - first_name: Niklas full_name: Byczkowicz, Niklas last_name: Byczkowicz - first_name: Abdelmoneim full_name: Eshra, Abdelmoneim last_name: Eshra - first_name: Jacqueline-Claire full_name: Montanaro-Punzengruber, Jacqueline-Claire id: 3786AB44-F248-11E8-B48F-1D18A9856A87 last_name: Montanaro-Punzengruber - first_name: Andrea full_name: Trevisiol, Andrea last_name: Trevisiol - first_name: Johannes full_name: Hirrlinger, Johannes last_name: Hirrlinger - first_name: Maarten Hp full_name: Kole, Maarten Hp last_name: Kole - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Stefan full_name: Hallermann, Stefan last_name: Hallermann citation: ama: Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, et al. HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. eLife. 2019;8. doi:10.7554/eLife.42766 apa: Byczkowicz, N., Eshra, A., Montanaro-Punzengruber, J.-C., Trevisiol, A., Hirrlinger, J., Kole, M. H., … Hallermann, S. (2019). HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.42766 chicago: Byczkowicz, Niklas, Abdelmoneim Eshra, Jacqueline-Claire Montanaro-Punzengruber, Andrea Trevisiol, Johannes Hirrlinger, Maarten Hp Kole, Ryuichi Shigemoto, and Stefan Hallermann. “HCN Channel-Mediated Neuromodulation Can Control Action Potential Velocity and Fidelity in Central Axons.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42766. ieee: N. Byczkowicz et al., “HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, Trevisiol A, Hirrlinger J, Kole MH, Shigemoto R, Hallermann S. 2019. HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. eLife. 8, e42766. mla: Byczkowicz, Niklas, et al. “HCN Channel-Mediated Neuromodulation Can Control Action Potential Velocity and Fidelity in Central Axons.” ELife, vol. 8, e42766, eLife Sciences Publications, 2019, doi:10.7554/eLife.42766. short: N. Byczkowicz, A. Eshra, J.-C. Montanaro-Punzengruber, A. Trevisiol, J. Hirrlinger, M.H. Kole, R. Shigemoto, S. Hallermann, ELife 8 (2019). date_created: 2019-09-15T22:00:43Z date_published: 2019-09-09T00:00:00Z date_updated: 2023-08-30T06:17:06Z day: '09' ddc: - '570' department: - _id: RySh doi: 10.7554/eLife.42766 external_id: isi: - '000485663900001' file: - access_level: open_access checksum: c350b7861ef0fb537cae8a3232aec016 content_type: application/pdf creator: dernst date_created: 2019-09-16T13:14:33Z date_updated: 2020-07-14T12:47:42Z file_id: '6880' file_name: 2019_eLife_Byczkowicz.pdf file_size: 4008137 relation: main_file file_date_updated: 2020-07-14T12:47:42Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: eLife publication_identifier: eissn: - 2050084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 8 year: '2019' ... --- _id: '7099' acknowledgement: "The authors thank Gabi Schmid for excellent technical support. We also thank\r\nDr. H. Harada, Dr. W. Kaufmann, and Dr. B. Kapelari for testing the specificity\r\nof some of the antibodies used in this study on replicas. Funding was provided\r\nby the Austrian Science Fund (Fonds zur Fo¨ rderung der Wissenschaftlichen\r\nForschung) Sonderforschungsbereich grants F44-17 (to F.jF.), F44-10 and\r\nP25375-B24 (to N.S.), and P26680 (to G.S.) and by the Novartis Research\r\nFoundation and the Swiss National Science Foundation (to A.L). We also thank\r\nProf. M. Capogna for reading a previous version of the manuscript." article_processing_charge: No article_type: original author: - first_name: Yu full_name: Kasugai, Yu last_name: Kasugai - first_name: Elisabeth full_name: Vogel, Elisabeth last_name: Vogel - first_name: Heide full_name: Hörtnagl, Heide last_name: Hörtnagl - first_name: Sabine full_name: Schönherr, Sabine last_name: Schönherr - first_name: Enrica full_name: Paradiso, Enrica last_name: Paradiso - first_name: Markus full_name: Hauschild, Markus last_name: Hauschild - first_name: Georg full_name: Göbel, Georg last_name: Göbel - first_name: Ivan full_name: Milenkovic, Ivan last_name: Milenkovic - first_name: Yvan full_name: Peterschmitt, Yvan last_name: Peterschmitt - first_name: Ramon full_name: Tasan, Ramon last_name: Tasan - first_name: Günther full_name: Sperk, Günther last_name: Sperk - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Werner full_name: Sieghart, Werner last_name: Sieghart - first_name: Nicolas full_name: Singewald, Nicolas last_name: Singewald - first_name: Andreas full_name: Lüthi, Andreas last_name: Lüthi - first_name: Francesco full_name: Ferraguti, Francesco last_name: Ferraguti citation: ama: Kasugai Y, Vogel E, Hörtnagl H, et al. Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning. Neuron. 2019;104(4):781-794.e4. doi:10.1016/j.neuron.2019.08.013 apa: Kasugai, Y., Vogel, E., Hörtnagl, H., Schönherr, S., Paradiso, E., Hauschild, M., … Ferraguti, F. (2019). Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.08.013 chicago: Kasugai, Yu, Elisabeth Vogel, Heide Hörtnagl, Sabine Schönherr, Enrica Paradiso, Markus Hauschild, Georg Göbel, et al. “Structural and Functional Remodeling of Amygdala GABAergic Synapses in Associative Fear Learning.” Neuron. Elsevier, 2019. https://doi.org/10.1016/j.neuron.2019.08.013. ieee: Y. Kasugai et al., “Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning,” Neuron, vol. 104, no. 4. Elsevier, p. 781–794.e4, 2019. ista: Kasugai Y, Vogel E, Hörtnagl H, Schönherr S, Paradiso E, Hauschild M, Göbel G, Milenkovic I, Peterschmitt Y, Tasan R, Sperk G, Shigemoto R, Sieghart W, Singewald N, Lüthi A, Ferraguti F. 2019. Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning. Neuron. 104(4), 781–794.e4. mla: Kasugai, Yu, et al. “Structural and Functional Remodeling of Amygdala GABAergic Synapses in Associative Fear Learning.” Neuron, vol. 104, no. 4, Elsevier, 2019, p. 781–794.e4, doi:10.1016/j.neuron.2019.08.013. short: Y. Kasugai, E. Vogel, H. Hörtnagl, S. Schönherr, E. Paradiso, M. Hauschild, G. Göbel, I. Milenkovic, Y. Peterschmitt, R. Tasan, G. Sperk, R. Shigemoto, W. Sieghart, N. Singewald, A. Lüthi, F. Ferraguti, Neuron 104 (2019) 781–794.e4. date_created: 2019-11-25T08:02:39Z date_published: 2019-11-20T00:00:00Z date_updated: 2023-08-30T07:28:22Z day: '20' ddc: - '571' - '599' department: - _id: RySh doi: 10.1016/j.neuron.2019.08.013 external_id: isi: - '000497963500017' pmid: - '31543297' has_accepted_license: '1' intvolume: ' 104' isi: 1 issue: '4' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.neuron.2019.08.013 month: '11' oa: 1 oa_version: Published Version page: 781-794.e4 pmid: 1 publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 104 year: '2019' ... --- _id: '7179' abstract: - lang: eng text: Glutamate is the major excitatory neurotransmitter in the CNS binding to a variety of glutamate receptors. Metabotropic glutamate receptors (mGluR1 to mGluR8) can act excitatory or inhibitory, depending on associated signal cascades. Expression and localization of inhibitory acting mGluRs at inner hair cells (IHCs) in the cochlea are largely unknown. Here, we analyzed expression of mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, and mGluR8 and investigated their localization with respect to the presynaptic ribbon of IHC synapses. We detected transcripts for mGluR2, mGluR3, and mGluR4 as well as for mGluR7a, mGluR7b, mGluR8a, and mGluR8b splice variants. Using receptor-specific antibodies in cochlear wholemounts, we found expression of mGluR2, mGluR4, and mGluR8b close to presynaptic ribbons. Super resolution and confocal microscopy in combination with 3-dimensional reconstructions indicated a postsynaptic localization of mGluR2 that overlaps with postsynaptic density protein 95 on dendrites of afferent type I spiral ganglion neurons. In contrast, mGluR4 and mGluR8b were expressed at the presynapse close to IHC ribbons. In summary, we localized in detail 3 mGluR types at IHC ribbon synapses, providing a fundament for new therapeutical strategies that could protect the cochlea against noxious stimuli and excitotoxicity. article_processing_charge: No article_type: original author: - first_name: Lisa full_name: Klotz, Lisa last_name: Klotz - first_name: Olaf full_name: Wendler, Olaf last_name: Wendler - first_name: Renato full_name: Frischknecht, Renato last_name: Frischknecht - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Holger full_name: Schulze, Holger last_name: Schulze - first_name: Ralf full_name: Enz, Ralf last_name: Enz citation: ama: Klotz L, Wendler O, Frischknecht R, Shigemoto R, Schulze H, Enz R. Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses. FASEB Journal. 2019;33(12):13734-13746. doi:10.1096/fj.201901543R apa: Klotz, L., Wendler, O., Frischknecht, R., Shigemoto, R., Schulze, H., & Enz, R. (2019). Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses. FASEB Journal. FASEB. https://doi.org/10.1096/fj.201901543R chicago: Klotz, Lisa, Olaf Wendler, Renato Frischknecht, Ryuichi Shigemoto, Holger Schulze, and Ralf Enz. “Localization of Group II and III Metabotropic Glutamate Receptors at Pre- and Postsynaptic Sites of Inner Hair Cell Ribbon Synapses.” FASEB Journal. FASEB, 2019. https://doi.org/10.1096/fj.201901543R. ieee: L. Klotz, O. Wendler, R. Frischknecht, R. Shigemoto, H. Schulze, and R. Enz, “Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses,” FASEB Journal, vol. 33, no. 12. FASEB, pp. 13734–13746, 2019. ista: Klotz L, Wendler O, Frischknecht R, Shigemoto R, Schulze H, Enz R. 2019. Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses. FASEB Journal. 33(12), 13734–13746. mla: Klotz, Lisa, et al. “Localization of Group II and III Metabotropic Glutamate Receptors at Pre- and Postsynaptic Sites of Inner Hair Cell Ribbon Synapses.” FASEB Journal, vol. 33, no. 12, FASEB, 2019, pp. 13734–46, doi:10.1096/fj.201901543R. short: L. Klotz, O. Wendler, R. Frischknecht, R. Shigemoto, H. Schulze, R. Enz, FASEB Journal 33 (2019) 13734–13746. date_created: 2019-12-15T23:00:42Z date_published: 2019-12-01T00:00:00Z date_updated: 2023-09-06T14:34:36Z day: '01' ddc: - '571' - '599' department: - _id: RySh doi: 10.1096/fj.201901543R external_id: isi: - '000507466100054' pmid: - '31585509' file: - access_level: open_access checksum: 79e3b72481dc32489911121cf3b7d8d0 content_type: application/pdf creator: shigemot date_created: 2020-12-06T17:30:09Z date_updated: 2020-12-06T17:30:09Z file_id: '8922' file_name: Klotz et al 2019 EMBO Reports.pdf file_size: 4766789 relation: main_file success: 1 file_date_updated: 2020-12-06T17:30:09Z has_accepted_license: '1' intvolume: ' 33' isi: 1 issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Submitted Version page: 13734-13746 pmid: 1 publication: FASEB Journal publication_identifier: eissn: - '15306860' publication_status: published publisher: FASEB quality_controlled: '1' scopus_import: '1' status: public title: Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 33 year: '2019' ... --- _id: '7398' abstract: - lang: eng text: 'Transporters of the solute carrier 6 (SLC6) family translocate their cognate substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4). Here, we posited that the transport cycle of individual SLC6 transporters reflects the physiological requirements they operate under. We tested this hypothesis by analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions in real time by electrophysiological recordings. Contrary to monoamine transporters, both GlyTs were found to have a high transport capacity driven by rapid return of the empty transporter after release of Cl− on the intracellular side. Rapid cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate ions and substrate such that their forward transport mode was maintained even under conditions of elevated intracellular Na+ or Cl−. The most important differences in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1 were governed by transition of the substrate-bound transporter from outward- to inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+ binding (or a related conformational change). Kinetic modeling showed that the kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels required for NMDA receptor activation.' article_processing_charge: No article_type: original author: - first_name: Fatma Asli full_name: Erdem, Fatma Asli last_name: Erdem - first_name: Marija full_name: Ilic, Marija last_name: Ilic - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Jakub full_name: Gołacki, Jakub last_name: Gołacki - first_name: Gert full_name: Lubec, Gert last_name: Lubec - first_name: Michael full_name: Freissmuth, Michael last_name: Freissmuth - first_name: Walter full_name: Sandtner, Walter last_name: Sandtner citation: ama: Erdem FA, Ilic M, Koppensteiner P, et al. A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. The Journal of General Physiology. 2019;151(8):1035-1050. doi:10.1085/jgp.201912318 apa: Erdem, F. A., Ilic, M., Koppensteiner, P., Gołacki, J., Lubec, G., Freissmuth, M., & Sandtner, W. (2019). A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. The Journal of General Physiology. Rockefeller University Press. https://doi.org/10.1085/jgp.201912318 chicago: Erdem, Fatma Asli, Marija Ilic, Peter Koppensteiner, Jakub Gołacki, Gert Lubec, Michael Freissmuth, and Walter Sandtner. “A Comparison of the Transport Kinetics of Glycine Transporter 1 and Glycine Transporter 2.” The Journal of General Physiology. Rockefeller University Press, 2019. https://doi.org/10.1085/jgp.201912318. ieee: F. A. Erdem et al., “A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2,” The Journal of General Physiology, vol. 151, no. 8. Rockefeller University Press, pp. 1035–1050, 2019. ista: Erdem FA, Ilic M, Koppensteiner P, Gołacki J, Lubec G, Freissmuth M, Sandtner W. 2019. A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. The Journal of General Physiology. 151(8), 1035–1050. mla: Erdem, Fatma Asli, et al. “A Comparison of the Transport Kinetics of Glycine Transporter 1 and Glycine Transporter 2.” The Journal of General Physiology, vol. 151, no. 8, Rockefeller University Press, 2019, pp. 1035–50, doi:10.1085/jgp.201912318. short: F.A. Erdem, M. Ilic, P. Koppensteiner, J. Gołacki, G. Lubec, M. Freissmuth, W. Sandtner, The Journal of General Physiology 151 (2019) 1035–1050. date_created: 2020-01-29T16:06:29Z date_published: 2019-07-03T00:00:00Z date_updated: 2023-09-07T14:52:23Z day: '03' ddc: - '570' department: - _id: RySh doi: 10.1085/jgp.201912318 external_id: isi: - '000478792500008' pmid: - '31270129' file: - access_level: open_access checksum: 5706b4ccd74ee3e50bf7ecb2a203df71 content_type: application/pdf creator: dernst date_created: 2020-02-05T07:20:32Z date_updated: 2020-07-14T12:47:57Z file_id: '7450' file_name: 2019_JGP_Erdem.pdf file_size: 2641297 relation: main_file file_date_updated: 2020-07-14T12:47:57Z has_accepted_license: '1' intvolume: ' 151' isi: 1 issue: '8' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1035-1050 pmid: 1 publication: The Journal of General Physiology publication_identifier: eissn: - 1540-7748 issn: - 0022-1295 publication_status: published publisher: Rockefeller University Press quality_controlled: '1' scopus_import: '1' status: public title: A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2 tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 151 year: '2019' ... --- _id: '7391' abstract: - lang: eng text: Electron microscopy (EM) is a technology that enables visualization of single proteins at a nanometer resolution. However, current protein analysis by EM mainly relies on immunolabeling with gold-particle-conjugated antibodies, which is compromised by large size of antibody, precluding precise detection of protein location in biological samples. Here, we develop a specific chemical labeling method for EM detection of proteins at single-molecular level. Rational design of α-helical peptide tag and probe structure provided a complementary reaction pair that enabled specific cysteine conjugation of the tag. The developed chemical labeling with gold-nanoparticle-conjugated probe showed significantly higher labeling efficiency and detectability of high-density clusters of tag-fused G protein-coupled receptors in freeze-fracture replicas compared with immunogold labeling. Furthermore, in ultrathin sections, the spatial resolution of the chemical labeling was significantly higher than that of antibody-mediated labeling. These results demonstrate substantial advantages of the chemical labeling approach for single protein visualization by EM. article_processing_charge: No article_type: original author: - first_name: Shigekazu full_name: Tabata, Shigekazu id: 4427179E-F248-11E8-B48F-1D18A9856A87 last_name: Tabata - first_name: Marijo full_name: Jevtic, Marijo id: 4BE3BC94-F248-11E8-B48F-1D18A9856A87 last_name: Jevtic - first_name: Nobutaka full_name: Kurashige, Nobutaka last_name: Kurashige - first_name: Hirokazu full_name: Fuchida, Hirokazu last_name: Fuchida - first_name: Munetsugu full_name: Kido, Munetsugu last_name: Kido - first_name: Kazushi full_name: Tani, Kazushi last_name: Tani - first_name: Naoki full_name: Zenmyo, Naoki last_name: Zenmyo - first_name: Shohei full_name: Uchinomiya, Shohei last_name: Uchinomiya - first_name: Harumi full_name: Harada, Harumi id: 2E55CDF2-F248-11E8-B48F-1D18A9856A87 last_name: Harada orcid: 0000-0001-7429-7896 - first_name: Makoto full_name: Itakura, Makoto last_name: Itakura - first_name: Itaru full_name: Hamachi, Itaru last_name: Hamachi - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Akio full_name: Ojida, Akio last_name: Ojida citation: ama: Tabata S, Jevtic M, Kurashige N, et al. Electron microscopic detection of single membrane proteins by a specific chemical labeling. iScience. 2019;22(12):256-268. doi:10.1016/j.isci.2019.11.025 apa: Tabata, S., Jevtic, M., Kurashige, N., Fuchida, H., Kido, M., Tani, K., … Ojida, A. (2019). Electron microscopic detection of single membrane proteins by a specific chemical labeling. IScience. Elsevier. https://doi.org/10.1016/j.isci.2019.11.025 chicago: Tabata, Shigekazu, Marijo Jevtic, Nobutaka Kurashige, Hirokazu Fuchida, Munetsugu Kido, Kazushi Tani, Naoki Zenmyo, et al. “Electron Microscopic Detection of Single Membrane Proteins by a Specific Chemical Labeling.” IScience. Elsevier, 2019. https://doi.org/10.1016/j.isci.2019.11.025. ieee: S. Tabata et al., “Electron microscopic detection of single membrane proteins by a specific chemical labeling,” iScience, vol. 22, no. 12. Elsevier, pp. 256–268, 2019. ista: Tabata S, Jevtic M, Kurashige N, Fuchida H, Kido M, Tani K, Zenmyo N, Uchinomiya S, Harada H, Itakura M, Hamachi I, Shigemoto R, Ojida A. 2019. Electron microscopic detection of single membrane proteins by a specific chemical labeling. iScience. 22(12), 256–268. mla: Tabata, Shigekazu, et al. “Electron Microscopic Detection of Single Membrane Proteins by a Specific Chemical Labeling.” IScience, vol. 22, no. 12, Elsevier, 2019, pp. 256–68, doi:10.1016/j.isci.2019.11.025. short: S. Tabata, M. Jevtic, N. Kurashige, H. Fuchida, M. Kido, K. Tani, N. Zenmyo, S. Uchinomiya, H. Harada, M. Itakura, I. Hamachi, R. Shigemoto, A. Ojida, IScience 22 (2019) 256–268. date_created: 2020-01-29T15:56:56Z date_published: 2019-12-20T00:00:00Z date_updated: 2024-03-27T23:30:13Z day: '20' ddc: - '570' department: - _id: RySh doi: 10.1016/j.isci.2019.11.025 ec_funded: 1 external_id: isi: - :000504652000020 pmid: - '31786521' file: - access_level: open_access checksum: f3e90056a49f09b205b1c4f8c739ffd1 content_type: application/pdf creator: dernst date_created: 2020-02-04T10:48:36Z date_updated: 2020-07-14T12:47:57Z file_id: '7448' file_name: 2019_iScience_Tabata.pdf file_size: 7197776 relation: main_file file_date_updated: 2020-07-14T12:47:57Z has_accepted_license: '1' intvolume: ' 22' issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 256-268 pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 25CBA828-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '720270' name: Human Brain Project Specific Grant Agreement 1 (HBP SGA 1) publication: iScience publication_identifier: issn: - 2589-0042 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '11393' relation: dissertation_contains status: public scopus_import: '1' status: public title: Electron microscopic detection of single membrane proteins by a specific chemical labeling tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 22 year: '2019' ... --- _id: '562' abstract: - lang: eng text: Primary neuronal cell culture preparations are widely used to investigate synaptic functions. This chapter describes a detailed protocol for the preparation of a neuronal cell culture in which giant calyx-type synaptic terminals are formed. This chapter also presents detailed protocols for utilizing the main technical advantages provided by such a preparation, namely, labeling and imaging of synaptic organelles and electrophysiological recordings directly from presynaptic terminals. alternative_title: - Methods in Molecular Biology article_processing_charge: No author: - first_name: Dimitar full_name: Dimitrov, Dimitar last_name: Dimitrov - first_name: Laurent full_name: Guillaud, Laurent last_name: Guillaud - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Tomoyuki full_name: Takahashi, Tomoyuki last_name: Takahashi citation: ama: 'Dimitrov D, Guillaud L, Eguchi K, Takahashi T. Culture of mouse giant central nervous system synapses and application for imaging and electrophysiological analyses. In: Skaper SD, ed. Neurotrophic Factors. Vol 1727. Springer; 2018:201-215. doi:10.1007/978-1-4939-7571-6_15' apa: Dimitrov, D., Guillaud, L., Eguchi, K., & Takahashi, T. (2018). Culture of mouse giant central nervous system synapses and application for imaging and electrophysiological analyses. In S. D. Skaper (Ed.), Neurotrophic Factors (Vol. 1727, pp. 201–215). Springer. https://doi.org/10.1007/978-1-4939-7571-6_15 chicago: Dimitrov, Dimitar, Laurent Guillaud, Kohgaku Eguchi, and Tomoyuki Takahashi. “Culture of Mouse Giant Central Nervous System Synapses and Application for Imaging and Electrophysiological Analyses.” In Neurotrophic Factors, edited by Stephen D. Skaper, 1727:201–15. Springer, 2018. https://doi.org/10.1007/978-1-4939-7571-6_15. ieee: D. Dimitrov, L. Guillaud, K. Eguchi, and T. Takahashi, “Culture of mouse giant central nervous system synapses and application for imaging and electrophysiological analyses,” in Neurotrophic Factors, vol. 1727, S. D. Skaper, Ed. Springer, 2018, pp. 201–215. ista: 'Dimitrov D, Guillaud L, Eguchi K, Takahashi T. 2018.Culture of mouse giant central nervous system synapses and application for imaging and electrophysiological analyses. In: Neurotrophic Factors. Methods in Molecular Biology, vol. 1727, 201–215.' mla: Dimitrov, Dimitar, et al. “Culture of Mouse Giant Central Nervous System Synapses and Application for Imaging and Electrophysiological Analyses.” Neurotrophic Factors, edited by Stephen D. Skaper, vol. 1727, Springer, 2018, pp. 201–15, doi:10.1007/978-1-4939-7571-6_15. short: D. Dimitrov, L. Guillaud, K. Eguchi, T. Takahashi, in:, S.D. Skaper (Ed.), Neurotrophic Factors, Springer, 2018, pp. 201–215. date_created: 2018-12-11T11:47:11Z date_published: 2018-01-01T00:00:00Z date_updated: 2021-01-12T08:03:05Z day: '01' ddc: - '570' department: - _id: RySh doi: 10.1007/978-1-4939-7571-6_15 editor: - first_name: Stephen D. full_name: Skaper, Stephen D. last_name: Skaper external_id: pmid: - '29222783' file: - access_level: open_access checksum: 8aa174ca65a56fbb19e9f88cff3ac3fd content_type: application/pdf creator: dernst date_created: 2019-11-19T07:47:43Z date_updated: 2020-07-14T12:47:09Z file_id: '7046' file_name: 2018_NeurotrophicFactors_Dimitrov.pdf file_size: 787407 relation: main_file file_date_updated: 2020-07-14T12:47:09Z has_accepted_license: '1' intvolume: ' 1727' language: - iso: eng month: '01' oa: 1 oa_version: Submitted Version page: 201 - 215 pmid: 1 publication: Neurotrophic Factors publication_status: published publisher: Springer publist_id: '7252' quality_controlled: '1' scopus_import: 1 status: public title: Culture of mouse giant central nervous system synapses and application for imaging and electrophysiological analyses type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1727 year: '2018' ... --- _id: '41' abstract: - lang: eng text: 'The small-conductance, Ca2+-activated K+ (SK) channel subtype SK2 regulates the spike rate and firing frequency, as well as Ca2+ transients in Purkinje cells (PCs). To understand the molecular basis by which SK2 channels mediate these functions, we analyzed the exact location and densities of SK2 channels along the neuronal surface of the mouse cerebellar PCs using SDS-digested freeze-fracture replica labeling (SDS-FRL) of high sensitivity combined with quantitative analyses. Immunogold particles for SK2 were observed on post- and pre-synaptic compartments showing both scattered and clustered distribution patterns. We found an axo-somato-dendritic gradient of the SK2 particle density increasing 12-fold from soma to dendritic spines. Using two different immunogold approaches, we also found that SK2 immunoparticles were frequently adjacent to, but never overlap with, the postsynaptic density of excitatory synapses in PC spines. Co-immunoprecipitation analysis demonstrated that SK2 channels form macromolecular complexes with two types of proteins that mobilize Ca2+: CaV2.1 channels and mGlu1α receptors in the cerebellum. Freeze-fracture replica double-labeling showed significant co-clustering of particles for SK2 with those for CaV2.1 channels and mGlu1α receptors. SK2 channels were also detected at presynaptic sites, mostly at the presynaptic active zone (AZ), where they are close to CaV2.1 channels, though they are not significantly co-clustered. These data demonstrate that SK2 channels located in different neuronal compartments can associate with distinct proteins mobilizing Ca2+, and suggest that the ultrastructural association of SK2 with CaV2.1 and mGlu1α provides the mechanism that ensures voltage (excitability) regulation by distinct intracellular Ca2+ transients in PCs.' article_number: '311' article_processing_charge: No article_type: original author: - first_name: Rafæl full_name: Luján, Rafæl last_name: Luján - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Francisco full_name: Ciruela, Francisco last_name: Ciruela - first_name: Xavier full_name: Arus, Xavier last_name: Arus - first_name: Alejandro full_name: Martín Belmonte, Alejandro last_name: Martín Belmonte - first_name: Rocío full_name: Alfaro Ruiz, Rocío last_name: Alfaro Ruiz - first_name: Jesus full_name: Martinez Gomez, Jesus last_name: Martinez Gomez - first_name: Luis full_name: De La Ossa, Luis last_name: De La Ossa - first_name: Masahiko full_name: Watanabe, Masahiko last_name: Watanabe - first_name: John full_name: Adelman, John last_name: Adelman - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa citation: ama: Luján R, Aguado C, Ciruela F, et al. Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells. Frontiers in Cellular Neuroscience. 2018;12. doi:10.3389/fncel.2018.00311 apa: Luján, R., Aguado, C., Ciruela, F., Arus, X., Martín Belmonte, A., Alfaro Ruiz, R., … Fukazawa, Y. (2018). Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells. Frontiers in Cellular Neuroscience. Frontiers Media. https://doi.org/10.3389/fncel.2018.00311 chicago: Luján, Rafæl, Carolina Aguado, Francisco Ciruela, Xavier Arus, Alejandro Martín Belmonte, Rocío Alfaro Ruiz, Jesus Martinez Gomez, et al. “Sk2 Channels Associate with MGlu1α Receptors and CaV2.1 Channels in Purkinje Cells.” Frontiers in Cellular Neuroscience. Frontiers Media, 2018. https://doi.org/10.3389/fncel.2018.00311. ieee: R. Luján et al., “Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells,” Frontiers in Cellular Neuroscience, vol. 12. Frontiers Media, 2018. ista: Luján R, Aguado C, Ciruela F, Arus X, Martín Belmonte A, Alfaro Ruiz R, Martinez Gomez J, De La Ossa L, Watanabe M, Adelman J, Shigemoto R, Fukazawa Y. 2018. Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells. Frontiers in Cellular Neuroscience. 12, 311. mla: Luján, Rafæl, et al. “Sk2 Channels Associate with MGlu1α Receptors and CaV2.1 Channels in Purkinje Cells.” Frontiers in Cellular Neuroscience, vol. 12, 311, Frontiers Media, 2018, doi:10.3389/fncel.2018.00311. short: R. Luján, C. Aguado, F. Ciruela, X. Arus, A. Martín Belmonte, R. Alfaro Ruiz, J. Martinez Gomez, L. De La Ossa, M. Watanabe, J. Adelman, R. Shigemoto, Y. Fukazawa, Frontiers in Cellular Neuroscience 12 (2018). date_created: 2018-12-11T11:44:19Z date_published: 2018-09-19T00:00:00Z date_updated: 2023-09-18T09:31:18Z day: '19' ddc: - '570' department: - _id: RySh doi: 10.3389/fncel.2018.00311 ec_funded: 1 external_id: isi: - '000445090100002' file: - access_level: open_access checksum: 0bcaec8d596162af0b7fe3f31325d480 content_type: application/pdf creator: dernst date_created: 2018-12-17T08:49:03Z date_updated: 2020-07-14T12:46:23Z file_id: '5684' file_name: fncel-12-00311.pdf file_size: 6834251 relation: main_file file_date_updated: 2020-07-14T12:46:23Z has_accepted_license: '1' intvolume: ' 12' isi: 1 language: - iso: eng month: '09' oa: 1 oa_version: Published Version project: - _id: 25CBA828-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '720270' name: Human Brain Project Specific Grant Agreement 1 (HBP SGA 1) publication: Frontiers in Cellular Neuroscience publication_identifier: issn: - '16625102' publication_status: published publisher: Frontiers Media publist_id: '8013' quality_controlled: '1' scopus_import: '1' status: public title: Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 12 year: '2018' ... --- _id: '326' abstract: - lang: eng text: Three-dimensional (3D) super-resolution microscopy technique structured illumination microscopy (SIM) imaging of dendritic spines along the dendrite has not been previously performed in fixed tissues, mainly due to deterioration of the stripe pattern of the excitation laser induced by light scattering and optical aberrations. To address this issue and solve these optical problems, we applied a novel clearing reagent, LUCID, to fixed brains. In SIM imaging, the penetration depth and the spatial resolution were improved in LUCID-treated slices, and 160-nm spatial resolution was obtained in a large portion of the imaging volume on a single apical dendrite. Furthermore, in a morphological analysis of spine heads of layer V pyramidal neurons (L5PNs) in the medial prefrontal cortex (mPFC) of chronic dexamethasone (Dex)-treated mice, SIM imaging revealed an altered distribution of spine forms that could not be detected by high-NA confocal imaging. Thus, super-resolution SIM imaging represents a promising high-throughput method for revealing spine morphologies in single dendrites. acknowledged_ssus: - _id: EM-Fac article_processing_charge: No author: - first_name: Kazuaki full_name: Sawada, Kazuaki last_name: Sawada - first_name: Ryosuke full_name: Kawakami, Ryosuke last_name: Kawakami - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Tomomi full_name: Nemoto, Tomomi last_name: Nemoto citation: ama: Sawada K, Kawakami R, Shigemoto R, Nemoto T. Super resolution structural analysis of dendritic spines using three-dimensional structured illumination microscopy in cleared mouse brain slices. European Journal of Neuroscience. 2018;47(9):1033-1042. doi:10.1111/ejn.13901 apa: Sawada, K., Kawakami, R., Shigemoto, R., & Nemoto, T. (2018). Super resolution structural analysis of dendritic spines using three-dimensional structured illumination microscopy in cleared mouse brain slices. European Journal of Neuroscience. Wiley. https://doi.org/10.1111/ejn.13901 chicago: Sawada, Kazuaki, Ryosuke Kawakami, Ryuichi Shigemoto, and Tomomi Nemoto. “Super Resolution Structural Analysis of Dendritic Spines Using Three-Dimensional Structured Illumination Microscopy in Cleared Mouse Brain Slices.” European Journal of Neuroscience. Wiley, 2018. https://doi.org/10.1111/ejn.13901. ieee: K. Sawada, R. Kawakami, R. Shigemoto, and T. Nemoto, “Super resolution structural analysis of dendritic spines using three-dimensional structured illumination microscopy in cleared mouse brain slices,” European Journal of Neuroscience, vol. 47, no. 9. Wiley, pp. 1033–1042, 2018. ista: Sawada K, Kawakami R, Shigemoto R, Nemoto T. 2018. Super resolution structural analysis of dendritic spines using three-dimensional structured illumination microscopy in cleared mouse brain slices. European Journal of Neuroscience. 47(9), 1033–1042. mla: Sawada, Kazuaki, et al. “Super Resolution Structural Analysis of Dendritic Spines Using Three-Dimensional Structured Illumination Microscopy in Cleared Mouse Brain Slices.” European Journal of Neuroscience, vol. 47, no. 9, Wiley, 2018, pp. 1033–42, doi:10.1111/ejn.13901. short: K. Sawada, R. Kawakami, R. Shigemoto, T. Nemoto, European Journal of Neuroscience 47 (2018) 1033–1042. date_created: 2018-12-11T11:45:50Z date_published: 2018-03-07T00:00:00Z date_updated: 2023-09-19T09:58:40Z day: '07' ddc: - '570' department: - _id: RySh doi: 10.1111/ejn.13901 external_id: isi: - '000431496400001' file: - access_level: open_access checksum: 98e901d8229e44aa8f3b51d248dedd09 content_type: application/pdf creator: dernst date_created: 2018-12-17T16:16:50Z date_updated: 2020-07-14T12:46:06Z file_id: '5721' file_name: 2018_EJN_Sawada.pdf file_size: 4850261 relation: main_file file_date_updated: 2020-07-14T12:46:06Z has_accepted_license: '1' intvolume: ' 47' isi: 1 issue: '9' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 1033 - 1042 publication: European Journal of Neuroscience publication_status: published publisher: Wiley publist_id: '7539' quality_controlled: '1' scopus_import: '1' status: public title: Super resolution structural analysis of dendritic spines using three-dimensional structured illumination microscopy in cleared mouse brain slices tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 47 year: '2018' ... --- _id: '705' abstract: - lang: eng text: Although dopamine receptors D1 and D2 play key roles in hippocampal function, their synaptic localization within the hippocampus has not been fully elucidated. In order to understand precise functions of pre- or postsynaptic dopamine receptors (DRs), the development of protocols to differentiate pre- and postsynaptic DRs is essential. So far, most studies on determination and quantification of DRs did not discriminate between subsynaptic localization. Therefore, the aim of the study was to generate a robust workflow for the localization of DRs. This work provides the basis for future work on hippocampal DRs, in light that DRs may have different functions at pre- or postsynaptic sites. Synaptosomes from rat hippocampi isolated by a sucrose gradient protocol were prepared for super-resolution direct stochastic optical reconstruction microscopy (dSTORM) using Bassoon as a presynaptic zone and Homer1 as postsynaptic density marker. Direct labeling of primary validated antibodies against dopamine receptors D1 (D1R) and D2 (D2R) with Alexa Fluor 594 enabled unequivocal assignment of D1R and D2R to both, pre- and postsynaptic sites. D1R immunoreactivity clusters were observed within the presynaptic active zone as well as at perisynaptic sites at the edge of the presynaptic active zone. The results may be useful for the interpretation of previous studies and the design of future work on DRs in the hippocampus. Moreover, the reduction of the complexity of brain tissue by the use of synaptosomal preparations and dSTORM technology may represent a useful tool for synaptic localization of brain proteins. article_processing_charge: No author: - first_name: Andras full_name: Miklosi, Andras last_name: Miklosi - first_name: Giorgia full_name: Del Favero, Giorgia last_name: Del Favero - first_name: Tanja full_name: Bulat, Tanja last_name: Bulat - first_name: Harald full_name: Höger, Harald last_name: Höger - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Doris full_name: Marko, Doris last_name: Marko - first_name: Gert full_name: Lubec, Gert last_name: Lubec citation: ama: Miklosi A, Del Favero G, Bulat T, et al. Super resolution microscopical localization of dopamine receptors 1 and 2 in rat hippocampal synaptosomes. Molecular Neurobiology. 2018;55(6):4857 – 4869. doi:10.1007/s12035-017-0688-y apa: Miklosi, A., Del Favero, G., Bulat, T., Höger, H., Shigemoto, R., Marko, D., & Lubec, G. (2018). Super resolution microscopical localization of dopamine receptors 1 and 2 in rat hippocampal synaptosomes. Molecular Neurobiology. Springer. https://doi.org/10.1007/s12035-017-0688-y chicago: Miklosi, Andras, Giorgia Del Favero, Tanja Bulat, Harald Höger, Ryuichi Shigemoto, Doris Marko, and Gert Lubec. “Super Resolution Microscopical Localization of Dopamine Receptors 1 and 2 in Rat Hippocampal Synaptosomes.” Molecular Neurobiology. Springer, 2018. https://doi.org/10.1007/s12035-017-0688-y. ieee: A. Miklosi et al., “Super resolution microscopical localization of dopamine receptors 1 and 2 in rat hippocampal synaptosomes,” Molecular Neurobiology, vol. 55, no. 6. Springer, pp. 4857 – 4869, 2018. ista: Miklosi A, Del Favero G, Bulat T, Höger H, Shigemoto R, Marko D, Lubec G. 2018. Super resolution microscopical localization of dopamine receptors 1 and 2 in rat hippocampal synaptosomes. Molecular Neurobiology. 55(6), 4857 – 4869. mla: Miklosi, Andras, et al. “Super Resolution Microscopical Localization of Dopamine Receptors 1 and 2 in Rat Hippocampal Synaptosomes.” Molecular Neurobiology, vol. 55, no. 6, Springer, 2018, pp. 4857 – 4869, doi:10.1007/s12035-017-0688-y. short: A. Miklosi, G. Del Favero, T. Bulat, H. Höger, R. Shigemoto, D. Marko, G. Lubec, Molecular Neurobiology 55 (2018) 4857 – 4869. date_created: 2018-12-11T11:48:02Z date_published: 2018-06-01T00:00:00Z date_updated: 2023-09-19T09:58:11Z day: '01' department: - _id: RySh doi: 10.1007/s12035-017-0688-y external_id: isi: - '000431991500025' intvolume: ' 55' isi: 1 issue: '6' language: - iso: eng month: '06' oa_version: None page: 4857 – 4869 publication: Molecular Neurobiology publication_status: published publisher: Springer publist_id: '6991' quality_controlled: '1' scopus_import: '1' status: public title: Super resolution microscopical localization of dopamine receptors 1 and 2 in rat hippocampal synaptosomes type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 55 year: '2018' ... --- _id: '163' abstract: - lang: eng text: For ultrafast fixation of biological samples to avoid artifacts, high-pressure freezing (HPF) followed by freeze substitution (FS) is preferred over chemical fixation at room temperature. After HPF, samples are maintained at low temperature during dehydration and fixation, while avoiding damaging recrystallization. This is a notoriously slow process. McDonald and Webb demonstrated, in 2011, that sample agitation during FS dramatically reduces the necessary time. Then, in 2015, we (H.G. and S.R.) introduced an agitation module into the cryochamber of an automated FS unit and demonstrated that the preparation of algae could be shortened from days to a couple of hours. We argued that variability in the processing, reproducibility, and safety issues are better addressed using automated FS units. For dissemination, we started low-cost manufacturing of agitation modules for two of the most widely used FS units, the Automatic Freeze Substitution Systems, AFS(1) and AFS2, from Leica Microsystems, using three dimensional (3D)-printing of the major components. To test them, several labs independently used the modules on a wide variety of specimens that had previously been processed by manual agitation, or without agitation. We demonstrate that automated processing with sample agitation saves time, increases flexibility with respect to sample requirements and protocols, and produces data of at least as good quality as other approaches. article_processing_charge: No article_type: original author: - first_name: Siegfried full_name: Reipert, Siegfried last_name: Reipert - first_name: Helmuth full_name: Goldammer, Helmuth last_name: Goldammer - first_name: Christine full_name: Richardson, Christine last_name: Richardson - first_name: Martin full_name: Goldberg, Martin last_name: Goldberg - first_name: Timothy full_name: Hawkins, Timothy last_name: Hawkins - first_name: Elena full_name: Hollergschwandtner, Elena id: 3C054040-F248-11E8-B48F-1D18A9856A87 last_name: Hollergschwandtner - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Sebastian full_name: Antreich, Sebastian last_name: Antreich - first_name: York full_name: Stierhof, York last_name: Stierhof citation: ama: 'Reipert S, Goldammer H, Richardson C, et al. Agitation modules: Flexible means to accelerate automated freeze substitution. Journal of Histochemistry and Cytochemistry. 2018;66(12):903-921. doi:10.1369/0022155418786698' apa: 'Reipert, S., Goldammer, H., Richardson, C., Goldberg, M., Hawkins, T., Saeckl, E., … Stierhof, Y. (2018). Agitation modules: Flexible means to accelerate automated freeze substitution. Journal of Histochemistry and Cytochemistry. SAGE Publications. https://doi.org/10.1369/0022155418786698' chicago: 'Reipert, Siegfried, Helmuth Goldammer, Christine Richardson, Martin Goldberg, Timothy Hawkins, Elena Saeckl, Walter Kaufmann, Sebastian Antreich, and York Stierhof. “Agitation Modules: Flexible Means to Accelerate Automated Freeze Substitution.” Journal of Histochemistry and Cytochemistry. SAGE Publications, 2018. https://doi.org/10.1369/0022155418786698.' ieee: 'S. Reipert et al., “Agitation modules: Flexible means to accelerate automated freeze substitution,” Journal of Histochemistry and Cytochemistry, vol. 66, no. 12. SAGE Publications, pp. 903–921, 2018.' ista: 'Reipert S, Goldammer H, Richardson C, Goldberg M, Hawkins T, Saeckl E, Kaufmann W, Antreich S, Stierhof Y. 2018. Agitation modules: Flexible means to accelerate automated freeze substitution. Journal of Histochemistry and Cytochemistry. 66(12), 903–921.' mla: 'Reipert, Siegfried, et al. “Agitation Modules: Flexible Means to Accelerate Automated Freeze Substitution.” Journal of Histochemistry and Cytochemistry, vol. 66, no. 12, SAGE Publications, 2018, pp. 903–21, doi:10.1369/0022155418786698.' short: S. Reipert, H. Goldammer, C. Richardson, M. Goldberg, T. Hawkins, E. Saeckl, W. Kaufmann, S. Antreich, Y. Stierhof, Journal of Histochemistry and Cytochemistry 66 (2018) 903–921. date_created: 2018-12-11T11:44:57Z date_published: 2018-12-01T00:00:00Z date_updated: 2023-10-17T08:42:24Z day: '01' department: - _id: RySh - _id: EM-Fac doi: 10.1369/0022155418786698 external_id: isi: - '000452277700005' pmid: - '29969056' intvolume: ' 66' isi: 1 issue: '12' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1369/0022155418786698 month: '12' oa: 1 oa_version: Published Version page: 903-921 pmid: 1 publication: Journal of Histochemistry and Cytochemistry publication_identifier: issn: - 0022-1554 publication_status: published publisher: SAGE Publications quality_controlled: '1' scopus_import: '1' status: public title: 'Agitation modules: Flexible means to accelerate automated freeze substitution' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 66 year: '2018' ... --- _id: '51' abstract: - lang: eng text: Asymmetries have long been known about in the central nervous system. From gross anatomical differences, such as the presence of the parapineal organ in only one hemisphere of the developing zebrafish, to more subtle differences in activity between both hemispheres, as seen in freely roaming animals or human participants under PET and fMRI imaging analysis. The presence of asymmetries has been demonstrated to have huge behavioural implications, with their disruption often leading to the generation of neurological disorders, memory problems, changes in personality, and in an organism's health and well-being. For my Ph.D. work I aimed to tackle two important avenues of research. The first being the process of input-side dependency in the hippocampus, with the goal of finding a key gene responsible for its development (Gene X). The second project was to do with experience-induced laterality formation in the hippocampus. Specifically, how laterality in the synapse density of the CA1 stratum radiatum (s.r.) could be induced purely through environmental enrichment. Through unilateral tracer injections into the CA3, I was able to selectively measure the properties of synapses within the CA1 and investigate how they differed based upon which hemisphere the presynaptic neurone originated. Having found the existence of a previously unreported reversed (left-isomerism) i.v. mutant, through morpholocal examination of labelled terminals in the CA1 s.r., I aimed to elucidate a key gene responsible for the process of left or right determination of inputs to the CA1 s.r.. This work relates to the previous finding of input-side dependent asymmetry in the wild-type rodent, where the origin of the projecting neurone to the CA1 will determine the morphology of a synapse, to a greater degree than the hemisphere in which the projection terminates. Using left- and right-isomerism i.v. mice, in combination with whole genome sequence analysis, I highlight Ena/VASP-like (Evl) as a potential target for Gene X. In relation to this topic, I also highlight my work in the recently published paper of how knockout of PirB can lead to a lack of input-side dependency in the murine hippocampus. For the second question, I show that the environmental enrichment paradigm will lead to an asymmetry in the synapse densities in the hippocampus of mice. I also highlight that the nature of the enrichment is of less consequence than the process of enrichment itself. I demonstrate that the CA3 region will dramatically alter its projection targets, in relation to environmental stimulation, with the asymmetry in synaptic density, caused by enrichment, relying heavily on commissural fibres. I also highlight the vital importance of input-side dependent asymmetry, as a necessary component of experience-dependent laterality formation in the CA1 s.r.. However, my results suggest that it isn't the only cause, as there appears to be a CA1 dependent mechanism also at play. Upon further investigation, I highlight the significant, and highly important, finding that the changes seen in the CA1 s.r. were predominantly caused through projections from the left-CA3, with the right-CA3 having less involvement in this mechanism. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Matthew J full_name: Case, Matthew J id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87 last_name: Case citation: ama: 'Case MJ. From the left to the right: A tale of asymmetries, environments, and hippocampal development. 2018. doi:10.15479/AT:ISTA:th_1032' apa: 'Case, M. J. (2018). From the left to the right: A tale of asymmetries, environments, and hippocampal development. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_1032' chicago: 'Case, Matthew J. “From the Left to the Right: A Tale of Asymmetries, Environments, and Hippocampal Development.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_1032.' ieee: 'M. J. Case, “From the left to the right: A tale of asymmetries, environments, and hippocampal development,” Institute of Science and Technology Austria, 2018.' ista: 'Case MJ. 2018. From the left to the right: A tale of asymmetries, environments, and hippocampal development. Institute of Science and Technology Austria.' mla: 'Case, Matthew J. From the Left to the Right: A Tale of Asymmetries, Environments, and Hippocampal Development. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_1032.' short: 'M.J. Case, From the Left to the Right: A Tale of Asymmetries, Environments, and Hippocampal Development, Institute of Science and Technology Austria, 2018.' date_created: 2018-12-11T11:44:22Z date_published: 2018-06-27T00:00:00Z date_updated: 2023-09-07T12:39:22Z day: '27' ddc: - '571' - '576' degree_awarded: PhD department: - _id: RySh doi: 10.15479/AT:ISTA:th_1032 file: - access_level: closed checksum: dcc7b55619d8509dd62b8e99d6cdee44 content_type: application/msword creator: dernst date_created: 2019-04-09T07:16:26Z date_updated: 2021-02-11T23:30:13Z embargo_to: open_access file_id: '6251' file_name: 2018_Thesis_Case_Source.doc file_size: 141270528 relation: source_file - access_level: open_access checksum: f69fdd5c8709c4e618aa8c1a1221153d content_type: application/pdf creator: dernst date_created: 2019-04-09T07:16:23Z date_updated: 2021-02-11T11:17:14Z embargo: 2019-07-05 file_id: '6252' file_name: 2018_Thesis_Case.pdf file_size: 15193621 relation: main_file file_date_updated: 2021-02-11T23:30:13Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '186' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '8003' pubrep_id: '1032' related_material: record: - id: '682' relation: part_of_dissertation status: public status: public supervisor: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 title: 'From the left to the right: A tale of asymmetries, environments, and hippocampal development' type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2018' ... --- _id: '612' abstract: - lang: eng text: Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines. To understand the spatial relationship of GABAB receptors with two key effector ion channels, the G protein-gated inwardly rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel, biochemical and immunohistochemical approaches were performed. Co-immunoprecipitation analysis demonstrated that GABAB receptors co-assembled with GIRK and CaV2.1 channels in the cerebellum. Using double-labelling immunoelectron microscopic techniques, co-clustering between GABAB1 and GIRK2 was detected in dendritic spines, whereas they were mainly segregated in the dendritic shafts. In contrast, co-clustering of GABAB1 and CaV2.1 was detected in dendritic shafts but not spines. Presynaptically, although no significant co-clustering of GABAB1 and GIRK2 or CaV2.1 channels was detected, inter-cluster distance for GABAB1 and GIRK2 was significantly smaller in the active zone than in the dendritic shafts, and that for GABAB1 and CaV2.1 was significantly smaller in the active zone than in the dendritic shafts and spines. Thus, GABAB receptors are associated with GIRK and CaV2.1 channels in different subcellular compartments. These data provide a better framework for understanding the different roles played by GABAB receptors and their effector ion channels in the cerebellar network. article_processing_charge: No article_type: original author: - first_name: Rafael full_name: Luján, Rafael last_name: Luján - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Francisco full_name: Ciruela, Francisco last_name: Ciruela - first_name: Javier full_name: Cózar, Javier last_name: Cózar - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Luis full_name: De La Ossa, Luis last_name: De La Ossa - first_name: Bernhard full_name: Bettler, Bernhard last_name: Bettler - first_name: Kevin full_name: Wickman, Kevin last_name: Wickman - first_name: Masahiko full_name: Watanabe, Masahiko last_name: Watanabe - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa citation: ama: Luján R, Aguado C, Ciruela F, et al. Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. 2018;223(3):1565-1587. doi:10.1007/s00429-017-1568-y apa: Luján, R., Aguado, C., Ciruela, F., Cózar, J., Kleindienst, D., De La Ossa, L., … Fukazawa, Y. (2018). Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. Springer. https://doi.org/10.1007/s00429-017-1568-y chicago: Luján, Rafael, Carolina Aguado, Francisco Ciruela, Javier Cózar, David Kleindienst, Luis De La Ossa, Bernhard Bettler, et al. “Differential Association of GABAB Receptors with Their Effector Ion Channels in Purkinje Cells.” Brain Structure and Function. Springer, 2018. https://doi.org/10.1007/s00429-017-1568-y. ieee: R. Luján et al., “Differential association of GABAB receptors with their effector ion channels in Purkinje cells,” Brain Structure and Function, vol. 223, no. 3. Springer, pp. 1565–1587, 2018. ista: Luján R, Aguado C, Ciruela F, Cózar J, Kleindienst D, De La Ossa L, Bettler B, Wickman K, Watanabe M, Shigemoto R, Fukazawa Y. 2018. Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. 223(3), 1565–1587. mla: Luján, Rafael, et al. “Differential Association of GABAB Receptors with Their Effector Ion Channels in Purkinje Cells.” Brain Structure and Function, vol. 223, no. 3, Springer, 2018, pp. 1565–87, doi:10.1007/s00429-017-1568-y. short: R. Luján, C. Aguado, F. Ciruela, J. Cózar, D. Kleindienst, L. De La Ossa, B. Bettler, K. Wickman, M. Watanabe, R. Shigemoto, Y. Fukazawa, Brain Structure and Function 223 (2018) 1565–1587. date_created: 2018-12-11T11:47:29Z date_published: 2018-04-01T00:00:00Z date_updated: 2024-03-27T23:30:30Z day: '01' ddc: - '571' department: - _id: RySh doi: 10.1007/s00429-017-1568-y ec_funded: 1 external_id: isi: - '000428419500030' file: - access_level: open_access checksum: a55b3103476ecb5f4f983d8801807e8b content_type: application/pdf creator: system date_created: 2018-12-12T10:15:36Z date_updated: 2020-07-14T12:47:20Z file_id: '5157' file_name: IST-2018-1013-v1+1_2018_Kleindienst_Differential.pdf file_size: 5542926 relation: main_file file_date_updated: 2020-07-14T12:47:20Z has_accepted_license: '1' intvolume: ' 223' isi: 1 issue: '3' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: 1565 - 1587 project: - _id: 25CBA828-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '720270' name: Human Brain Project Specific Grant Agreement 1 (HBP SGA 1) - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Brain Structure and Function publication_status: published publisher: Springer publist_id: '7192' pubrep_id: '1013' quality_controlled: '1' related_material: record: - id: '9562' relation: dissertation_contains status: public scopus_import: '1' status: public title: Differential association of GABAB receptors with their effector ion channels in Purkinje cells tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 223 year: '2018' ... --- _id: '643' abstract: - lang: eng text: It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests (GTT) were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests (ITT) were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H2O2 levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H2O2 generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance. article_processing_charge: No article_type: original author: - first_name: Wuping full_name: Sun, Wuping last_name: Sun - first_name: Ming-Zhu full_name: Zhai, Ming-Zhu id: 34009CFA-F248-11E8-B48F-1D18A9856A87 last_name: Zhai - first_name: Qian full_name: Zhou, Qian last_name: Zhou - first_name: Chengrui full_name: Qian, Chengrui last_name: Qian - first_name: Changyu full_name: Jiang, Changyu last_name: Jiang citation: ama: Sun W, Zhai M-Z, Zhou Q, Qian C, Jiang C. Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats. Chinese Journal of Physiology. 2017;60(4):207-214. doi:10.4077/CJP.2017.BAF469 apa: Sun, W., Zhai, M.-Z., Zhou, Q., Qian, C., & Jiang, C. (2017). Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats. Chinese Journal of Physiology. Chinese Physiological Society. https://doi.org/10.4077/CJP.2017.BAF469 chicago: Sun, Wuping, Ming-Zhu Zhai, Qian Zhou, Chengrui Qian, and Changyu Jiang. “Effects of B Vitamins Overload on Plasma Insulin Level and Hydrogen Peroxide Generation in Rats.” Chinese Journal of Physiology. Chinese Physiological Society, 2017. https://doi.org/10.4077/CJP.2017.BAF469. ieee: W. Sun, M.-Z. Zhai, Q. Zhou, C. Qian, and C. Jiang, “Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats,” Chinese Journal of Physiology, vol. 60, no. 4. Chinese Physiological Society, pp. 207–214, 2017. ista: Sun W, Zhai M-Z, Zhou Q, Qian C, Jiang C. 2017. Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats. Chinese Journal of Physiology. 60(4), 207–214. mla: Sun, Wuping, et al. “Effects of B Vitamins Overload on Plasma Insulin Level and Hydrogen Peroxide Generation in Rats.” Chinese Journal of Physiology, vol. 60, no. 4, Chinese Physiological Society, 2017, pp. 207–14, doi:10.4077/CJP.2017.BAF469. short: W. Sun, M.-Z. Zhai, Q. Zhou, C. Qian, C. Jiang, Chinese Journal of Physiology 60 (2017) 207–214. date_created: 2018-12-11T11:47:40Z date_published: 2017-08-31T00:00:00Z date_updated: 2021-01-12T08:07:28Z day: '31' ddc: - '570' department: - _id: RySh doi: 10.4077/CJP.2017.BAF469 external_id: pmid: - '28847140' intvolume: ' 60' issue: '4' language: - iso: eng month: '08' oa_version: Published Version page: 207 - 214 pmid: 1 publication: Chinese Journal of Physiology publication_identifier: issn: - '03044920' publication_status: published publisher: Chinese Physiological Society publist_id: '7142' quality_controlled: '1' scopus_import: 1 status: public title: Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 60 year: '2017' ... --- _id: '693' abstract: - lang: eng text: 'Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such “simple synapses” indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Cav2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1–10) and 2.03 at 4 wk (range: 1–4), whereas the mean numbers of Cav2.1 clusters were 2.84 at 2 wk (range: 1–8) and 2.37 at 4 wk (range: 1–5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm2 to 0.0234 μm2), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels. ' article_processing_charge: Yes (in subscription journal) author: - first_name: Takafumi full_name: Miki, Takafumi last_name: Miki - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Gerardo full_name: Malagon, Gerardo last_name: Malagon - first_name: Laura full_name: Gomez, Laura last_name: Gomez - first_name: Katsuhiko full_name: Tabuchi, Katsuhiko last_name: Tabuchi - first_name: Masahiko full_name: Watanabe, Masahiko last_name: Watanabe - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Alain full_name: Marty, Alain last_name: Marty citation: ama: Miki T, Kaufmann W, Malagon G, et al. Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses. PNAS. 2017;114(26):E5246-E5255. doi:10.1073/pnas.1704470114 apa: Miki, T., Kaufmann, W., Malagon, G., Gomez, L., Tabuchi, K., Watanabe, M., … Marty, A. (2017). Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1704470114 chicago: Miki, Takafumi, Walter Kaufmann, Gerardo Malagon, Laura Gomez, Katsuhiko Tabuchi, Masahiko Watanabe, Ryuichi Shigemoto, and Alain Marty. “Numbers of Presynaptic Ca2+ Channel Clusters Match Those of Functionally Defined Vesicular Docking Sites in Single Central Synapses.” PNAS. National Academy of Sciences, 2017. https://doi.org/10.1073/pnas.1704470114. ieee: T. Miki et al., “Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses,” PNAS, vol. 114, no. 26. National Academy of Sciences, pp. E5246–E5255, 2017. ista: Miki T, Kaufmann W, Malagon G, Gomez L, Tabuchi K, Watanabe M, Shigemoto R, Marty A. 2017. Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses. PNAS. 114(26), E5246–E5255. mla: Miki, Takafumi, et al. “Numbers of Presynaptic Ca2+ Channel Clusters Match Those of Functionally Defined Vesicular Docking Sites in Single Central Synapses.” PNAS, vol. 114, no. 26, National Academy of Sciences, 2017, pp. E5246–55, doi:10.1073/pnas.1704470114. short: T. Miki, W. Kaufmann, G. Malagon, L. Gomez, K. Tabuchi, M. Watanabe, R. Shigemoto, A. Marty, PNAS 114 (2017) E5246–E5255. date_created: 2018-12-11T11:47:57Z date_published: 2017-06-27T00:00:00Z date_updated: 2023-02-23T12:54:57Z day: '27' ddc: - '570' department: - _id: EM-Fac - _id: RySh doi: 10.1073/pnas.1704470114 external_id: pmid: - '28607047' file: - access_level: open_access checksum: 2ab75d554f3df4a34d20fa8040589b7e content_type: application/pdf creator: kschuh date_created: 2020-01-03T13:27:29Z date_updated: 2020-07-14T12:47:44Z file_id: '7223' file_name: 2017_PNAS_Miki.pdf file_size: 2721544 relation: main_file file_date_updated: 2020-07-14T12:47:44Z has_accepted_license: '1' intvolume: ' 114' issue: '26' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: E5246 - E5255 pmid: 1 publication: PNAS publication_identifier: issn: - '00278424' publication_status: published publisher: National Academy of Sciences publist_id: '7013' quality_controlled: '1' scopus_import: 1 status: public title: Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 114 year: '2017' ... --- _id: '709' abstract: - lang: eng text: Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) share the similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using reverse transcriptase-quantitative PCRs (RT-qPCR). The results demonstrated that all 10 thermoTRPs are expressed in both iBAT and sWAT, and without significant difference in the mRNA expression level of thermoTRPs between these two tissues. Moreover, Trpv1 and Trpv3 mRNA expression levels in both iBAT and sWAT were significantly decreased in high fat diet (HFD)-induced obese mice and db/db (leptin receptor deficient) mice. Trpm2 mRNA expression level was significantly decreased only in sWAT from HFD-induced obese mice and db/db mice. On the other hand, Trpv2 and Trpv4 mRNA expression levels in iBAT and sWAT were significantly increased in HFD-induced obese mice and db/db mice. Taken together, we conclude that all 10 thermoTRPs are expressed in iBAT and sWAT. And several thermoTRPs differentially expressed in adipose tissues from HFD-induced obese mice and db/db mice, suggesting a potential involvement in anti-obesity regulations. author: - first_name: Wuping full_name: Sun, Wuping last_name: Sun - first_name: Chen full_name: Li, Chen last_name: Li - first_name: Yonghong full_name: Zhang, Yonghong last_name: Zhang - first_name: Changyu full_name: Jiang, Changyu last_name: Jiang - first_name: Ming-Zhu full_name: Zhai, Ming-Zhu id: 34009CFA-F248-11E8-B48F-1D18A9856A87 last_name: Zhai - first_name: Qian full_name: Zhou, Qian last_name: Zhou - first_name: Lizu full_name: Xiao, Lizu last_name: Xiao - first_name: Qiwen full_name: Deng, Qiwen last_name: Deng citation: ama: Sun W, Li C, Zhang Y, et al. Gene expression changes of thermo sensitive transient receptor potential channels in obese mice. Cell Biology International. 2017;41(8):908-913. doi:10.1002/cbin.10783 apa: Sun, W., Li, C., Zhang, Y., Jiang, C., Zhai, M.-Z., Zhou, Q., … Deng, Q. (2017). Gene expression changes of thermo sensitive transient receptor potential channels in obese mice. Cell Biology International. Wiley-Blackwell. https://doi.org/10.1002/cbin.10783 chicago: Sun, Wuping, Chen Li, Yonghong Zhang, Changyu Jiang, Ming-Zhu Zhai, Qian Zhou, Lizu Xiao, and Qiwen Deng. “Gene Expression Changes of Thermo Sensitive Transient Receptor Potential Channels in Obese Mice.” Cell Biology International. Wiley-Blackwell, 2017. https://doi.org/10.1002/cbin.10783. ieee: W. Sun et al., “Gene expression changes of thermo sensitive transient receptor potential channels in obese mice,” Cell Biology International, vol. 41, no. 8. Wiley-Blackwell, pp. 908–913, 2017. ista: Sun W, Li C, Zhang Y, Jiang C, Zhai M-Z, Zhou Q, Xiao L, Deng Q. 2017. Gene expression changes of thermo sensitive transient receptor potential channels in obese mice. Cell Biology International. 41(8), 908–913. mla: Sun, Wuping, et al. “Gene Expression Changes of Thermo Sensitive Transient Receptor Potential Channels in Obese Mice.” Cell Biology International, vol. 41, no. 8, Wiley-Blackwell, 2017, pp. 908–13, doi:10.1002/cbin.10783. short: W. Sun, C. Li, Y. Zhang, C. Jiang, M.-Z. Zhai, Q. Zhou, L. Xiao, Q. Deng, Cell Biology International 41 (2017) 908–913. date_created: 2018-12-11T11:48:04Z date_published: 2017-08-01T00:00:00Z date_updated: 2021-01-12T08:11:47Z day: '01' department: - _id: RySh doi: 10.1002/cbin.10783 intvolume: ' 41' issue: '8' language: - iso: eng month: '08' oa_version: None page: 908 - 913 publication: Cell Biology International publication_identifier: issn: - '10656995' publication_status: published publisher: Wiley-Blackwell publist_id: '6981' quality_controlled: '1' scopus_import: 1 status: public title: Gene expression changes of thermo sensitive transient receptor potential channels in obese mice type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 41 year: '2017' ... --- _id: '736' abstract: - lang: eng text: The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner. article_processing_charge: No author: - first_name: María full_name: Rubio, María last_name: Rubio - first_name: Ko full_name: Matsui, Ko last_name: Matsui - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Naomi full_name: Kamasawa, Naomi last_name: Kamasawa - first_name: Harumi full_name: Harada, Harumi id: 2E55CDF2-F248-11E8-B48F-1D18A9856A87 last_name: Harada orcid: 0000-0001-7429-7896 - first_name: Makoto full_name: Itakura, Makoto last_name: Itakura - first_name: Elek full_name: Molnár, Elek last_name: Molnár - first_name: Manabu full_name: Abe, Manabu last_name: Abe - first_name: Kenji full_name: Sakimura, Kenji last_name: Sakimura - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Rubio M, Matsui K, Fukazawa Y, et al. The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells. Brain Structure and Function. 2017;222(8):3375-3393. doi:10.1007/s00429-017-1408-0 apa: Rubio, M., Matsui, K., Fukazawa, Y., Kamasawa, N., Harada, H., Itakura, M., … Shigemoto, R. (2017). The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells. Brain Structure and Function. Springer. https://doi.org/10.1007/s00429-017-1408-0 chicago: Rubio, María, Ko Matsui, Yugo Fukazawa, Naomi Kamasawa, Harumi Harada, Makoto Itakura, Elek Molnár, Manabu Abe, Kenji Sakimura, and Ryuichi Shigemoto. “The Number and Distribution of AMPA Receptor Channels Containing Fast Kinetic GluA3 and GluA4 Subunits at Auditory Nerve Synapses Depend on the Target Cells.” Brain Structure and Function. Springer, 2017. https://doi.org/10.1007/s00429-017-1408-0. ieee: M. Rubio et al., “The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells,” Brain Structure and Function, vol. 222, no. 8. Springer, pp. 3375–3393, 2017. ista: Rubio M, Matsui K, Fukazawa Y, Kamasawa N, Harada H, Itakura M, Molnár E, Abe M, Sakimura K, Shigemoto R. 2017. The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells. Brain Structure and Function. 222(8), 3375–3393. mla: Rubio, María, et al. “The Number and Distribution of AMPA Receptor Channels Containing Fast Kinetic GluA3 and GluA4 Subunits at Auditory Nerve Synapses Depend on the Target Cells.” Brain Structure and Function, vol. 222, no. 8, Springer, 2017, pp. 3375–93, doi:10.1007/s00429-017-1408-0. short: M. Rubio, K. Matsui, Y. Fukazawa, N. Kamasawa, H. Harada, M. Itakura, E. Molnár, M. Abe, K. Sakimura, R. Shigemoto, Brain Structure and Function 222 (2017) 3375–3393. date_created: 2018-12-11T11:48:14Z date_published: 2017-11-01T00:00:00Z date_updated: 2023-09-27T14:14:51Z day: '01' ddc: - '571' department: - _id: RySh doi: 10.1007/s00429-017-1408-0 external_id: isi: - '000414761700002' file: - access_level: open_access checksum: 73787a22507de8fb585bb598e1418ca7 content_type: application/pdf creator: system date_created: 2018-12-12T10:10:20Z date_updated: 2020-07-14T12:47:56Z file_id: '4806' file_name: IST-2017-881-v1+1_s00429-017-1408-0.pdf file_size: 4011126 relation: main_file file_date_updated: 2020-07-14T12:47:56Z has_accepted_license: '1' intvolume: ' 222' isi: 1 issue: '8' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: 3375 - 3393 publication: Brain Structure and Function publication_identifier: issn: - '18632653' publication_status: published publisher: Springer publist_id: '6932' pubrep_id: '881' quality_controlled: '1' scopus_import: '1' status: public title: The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 222 year: '2017' ... --- _id: '740' abstract: - lang: eng text: 'Developments in bioengineering and molecular biology have introduced a palette of genetically encoded probes for identification of specific cell populations in electron microscopy. These probes can be targeted to distinct cellular compartments, rendering them electron dense through a subsequent chemical reaction. These electron densities strongly increase the local contrast in samples prepared for electron microscopy, allowing three major advances in ultrastructural mapping of circuits: genetic identification of circuit components, targeted imaging of regions of interest and automated analysis of the tagged circuits. Together, the gains from these advances can decrease the time required for the analysis of targeted circuit motifs by over two orders of magnitude. These genetic encoded tags for electron microscopy promise to simplify the analysis of circuit motifs and become a central tool for structure‐function studies of synaptic connections in the brain. We review the current state‐of‐the‐art with an emphasis on connectomics, the quantitative analysis of neuronal structures and motifs.' article_number: e288 article_processing_charge: No article_type: original author: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Maximilian A full_name: Jösch, Maximilian A id: 2BD278E6-F248-11E8-B48F-1D18A9856A87 last_name: Jösch orcid: 0000-0002-3937-1330 citation: ama: Shigemoto R, Jösch MA. The genetic encoded toolbox for electron microscopy and connectomics. WIREs Developmental Biology. 2017;6(6). doi:10.1002/wdev.288 apa: Shigemoto, R., & Jösch, M. A. (2017). The genetic encoded toolbox for electron microscopy and connectomics. WIREs Developmental Biology. Wiley-Blackwell. https://doi.org/10.1002/wdev.288 chicago: Shigemoto, Ryuichi, and Maximilian A Jösch. “The Genetic Encoded Toolbox for Electron Microscopy and Connectomics.” WIREs Developmental Biology. Wiley-Blackwell, 2017. https://doi.org/10.1002/wdev.288. ieee: R. Shigemoto and M. A. Jösch, “The genetic encoded toolbox for electron microscopy and connectomics,” WIREs Developmental Biology, vol. 6, no. 6. Wiley-Blackwell, 2017. ista: Shigemoto R, Jösch MA. 2017. The genetic encoded toolbox for electron microscopy and connectomics. WIREs Developmental Biology. 6(6), e288. mla: Shigemoto, Ryuichi, and Maximilian A. Jösch. “The Genetic Encoded Toolbox for Electron Microscopy and Connectomics.” WIREs Developmental Biology, vol. 6, no. 6, e288, Wiley-Blackwell, 2017, doi:10.1002/wdev.288. short: R. Shigemoto, M.A. Jösch, WIREs Developmental Biology 6 (2017). date_created: 2018-12-11T11:48:15Z date_published: 2017-08-11T00:00:00Z date_updated: 2023-09-27T12:51:41Z day: '11' ddc: - '570' department: - _id: RySh - _id: MaJö doi: 10.1002/wdev.288 external_id: isi: - '000412827400005' pmid: - '28800674' file: - access_level: open_access checksum: a9370f27b1591773b7a0de299bc81c8c content_type: application/pdf creator: dernst date_created: 2019-11-19T07:36:18Z date_updated: 2020-07-14T12:47:57Z file_id: '7045' file_name: 2017_WIREs_Shigemoto.pdf file_size: 1647787 relation: main_file file_date_updated: 2020-07-14T12:47:57Z has_accepted_license: '1' intvolume: ' 6' isi: 1 issue: '6' language: - iso: eng month: '08' oa: 1 oa_version: Submitted Version pmid: 1 publication: WIREs Developmental Biology publication_identifier: issn: - '17597684' publication_status: published publisher: Wiley-Blackwell publist_id: '6927' quality_controlled: '1' scopus_import: '1' status: public title: The genetic encoded toolbox for electron microscopy and connectomics tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 6 year: '2017' ...