[{"publication_status":"published","department":[{"_id":"SiHi"},{"_id":"RySh"}],"publisher":"Elsevier","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. ","year":"2024","pmid":1,"date_updated":"2024-03-05T09:43:02Z","date_created":"2023-04-27T09:41:48Z","volume":112,"author":[{"first_name":"Giselle T","last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T"},{"full_name":"Pauler, Florian","last_name":"Pauler","first_name":"Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Koppensteiner","first_name":"Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter"},{"full_name":"Krausgruber, Thomas","first_name":"Thomas","last_name":"Krausgruber"},{"full_name":"Streicher, Carmen","first_name":"Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schrammel, Martin","id":"f13e7cae-e8bd-11ed-841a-96dedf69f46d","last_name":"Schrammel","first_name":"Martin"},{"id":"e68ece33-f6e0-11ea-865d-ae1031dcc090","first_name":"Natalie Y","last_name":"Özgen","full_name":"Özgen, Natalie Y"},{"full_name":"Ivec, Alexis","id":"1d144691-e8be-11ed-9b33-bdd3077fad4c","first_name":"Alexis","last_name":"Ivec"},{"full_name":"Bock, Christoph","last_name":"Bock","first_name":"Christoph"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"}],"related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-pedigree-of-brain-cells/","description":"News on ISTA Website","relation":"press_release"}]},"file_date_updated":"2024-02-06T13:56:15Z","quality_controlled":"1","project":[{"name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F07805"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["38096816"]},"oa":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"PreCl"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2023.11.009","month":"01","publication_identifier":{"issn":["0896-6273"]},"status":"public","title":"Multipotent progenitors instruct ontogeny of the superior colliculus","ddc":["570"],"intvolume":" 112","_id":"12875","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"relation":"main_file","file_id":"14944","date_created":"2024-02-06T13:56:15Z","date_updated":"2024-02-06T13:56:15Z","checksum":"32b3788f7085cf44a84108d8faaff3ce","success":1,"file_name":"2024_Neuron_Cheung.pdf","access_level":"open_access","content_type":"application/pdf","file_size":5942467,"creator":"dernst"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"2","article_type":"original","page":"230-246.e11","publication":"Neuron","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","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.","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","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.","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.","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."},"date_published":"2024-01-17T00:00:00Z","scopus_import":"1","day":"17","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1"},{"ec_funded":1,"file_date_updated":"2024-03-12T13:42:42Z","article_number":"e2301449121","volume":121,"date_updated":"2024-03-12T13:44:18Z","date_created":"2024-03-05T09:23:55Z","related_material":{"link":[{"relation":"press_release","description":"News on ISTA Website","url":"https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/"}],"record":[{"relation":"research_data","status":"public","id":"13173"}]},"author":[{"full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","first_name":"Peter"},{"full_name":"Bhandari, Pradeep","last_name":"Bhandari","first_name":"Pradeep","orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Önal, Hüseyin C","orcid":"0000-0002-2771-2011","id":"4659D740-F248-11E8-B48F-1D18A9856A87","last_name":"Önal","first_name":"Hüseyin C"},{"full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane","first_name":"Carolina"},{"last_name":"Le Monnier","first_name":"Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","full_name":"Le Monnier, Elodie"},{"full_name":"Roy, Utsa","id":"4d26cf11-5355-11ee-ae5a-eb05e255b9b2","last_name":"Roy","first_name":"Utsa"},{"last_name":"Nakamura","first_name":"Yukihiro","full_name":"Nakamura, Yukihiro"},{"full_name":"Sadakata, Tetsushi","last_name":"Sadakata","first_name":"Tetsushi"},{"first_name":"Makoto","last_name":"Sanbo","full_name":"Sanbo, Makoto"},{"full_name":"Hirabayashi, Masumi","last_name":"Hirabayashi","first_name":"Masumi"},{"last_name":"Rhee","first_name":"JeongSeop","full_name":"Rhee, JeongSeop"},{"last_name":"Brose","first_name":"Nils","full_name":"Brose, Nils"},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas"},{"last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"}],"publisher":"Proceedings of the National Academy of Sciences","department":[{"_id":"RySh"},{"_id":"PeJo"}],"publication_status":"published","pmid":1,"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.","year":"2024","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"month":"02","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"doi":"10.1073/pnas.2301449121","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020"},{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020"}],"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"external_id":{"pmid":["38346189"]},"issue":"8","abstract":[{"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.","lang":"eng"}],"type":"journal_article","file":[{"relation":"main_file","file_id":"15110","date_updated":"2024-03-12T13:42:42Z","date_created":"2024-03-12T13:42:42Z","checksum":"b25b2a057c266ff317a48b0d54d6fc8a","success":1,"file_name":"2024_PNAS_Koppensteiner.pdf","access_level":"open_access","content_type":"application/pdf","file_size":13648221,"creator":"dernst"}],"oa_version":"Published Version","intvolume":" 121","status":"public","ddc":["570"],"title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"15084","article_processing_charge":"Yes (in subscription journal)","has_accepted_license":"1","day":"20","date_published":"2024-02-20T00:00:00Z","article_type":"original","citation":{"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.","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).","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.","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","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.","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"},"publication":"Proceedings of the National Academy of Sciences"},{"ec_funded":1,"publisher":"Elsevier","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"publication_status":"inpress","pmid":1,"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.","year":"2024","date_updated":"2024-03-14T13:14:18Z","date_created":"2024-01-21T23:00:56Z","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"15101"}],"link":[{"url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/","description":"News on ISTA Website","relation":"press_release"}]},"author":[{"first_name":"JingJing","last_name":"Chen","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, JingJing"},{"last_name":"Kaufmann","first_name":"Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","full_name":"Kaufmann, Walter"},{"full_name":"Chen, Chong","last_name":"Chen","first_name":"Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Itaru","last_name":"Arai","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","full_name":"Arai, Itaru"},{"first_name":"Olena","last_name":"Kim","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","full_name":"Kim, Olena"},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jonas, Peter M","first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"}],"publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"month":"01","project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"},{"grant_number":"25383","_id":"26B66A3E-B435-11E9-9278-68D0E5697425","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse"}],"quality_controlled":"1","external_id":{"pmid":["38215739"]},"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"doi":"10.1016/j.neuron.2023.12.002","type":"journal_article","abstract":[{"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.","lang":"eng"}],"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","status":"public","_id":"14843","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"None","scopus_import":"1","article_processing_charge":"No","day":"11","article_type":"original","citation":{"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.","short":"J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron (n.d.).","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.","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","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.","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"},"publication":"Neuron","date_published":"2024-01-11T00:00:00Z"},{"date_published":"2023-04-06T00:00:00Z","citation":{"short":"C. Alcarva, Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning, Institute of Science and Technology Austria, 2023.","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.","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.","ama":"Alcarva C. Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. 2023. doi: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.","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","ista":"Alcarva C. 2023. Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. Institute of Science and Technology Austria."},"page":"115","day":"06","article_processing_charge":"No","has_accepted_license":"1","oa_version":"Published Version","file":[{"creator":"cchlebak","file_size":9881969,"content_type":"application/pdf","file_name":"Thesis_CatarinaAlcarva_final pdfA.pdf","embargo_to":"open_access","access_level":"closed","date_updated":"2023-04-07T06:16:06Z","date_created":"2023-04-07T06:16:06Z","checksum":"35b5997d2b0acb461f9d33d073da0df5","file_id":"12814","embargo":"2024-04-07","relation":"main_file"},{"relation":"source_file","file_id":"12815","checksum":"81198f63c294890f6d58e8b29782efdc","date_created":"2023-04-07T06:17:11Z","date_updated":"2023-04-07T06:17:11Z","access_level":"closed","file_name":"Thesis_CatarinaAlcarva_final_for printing.pdf","file_size":44201583,"content_type":"application/pdf","creator":"cchlebak"},{"access_level":"closed","file_name":"Thesis_CatarinaAlcarva_final.docx","creator":"cchlebak","file_size":84731244,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"12816","relation":"source_file","checksum":"0317bf7f457bb585f99d453ffa69eb53","date_updated":"2023-04-07T06:18:05Z","date_created":"2023-04-07T06:18:05Z"}],"_id":"12809","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","ddc":["570"],"title":"Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning","status":"public","abstract":[{"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. ","lang":"eng"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"doi":"10.15479/at:ista:12809","degree_awarded":"PhD","supervisor":[{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"PreCl"}],"language":[{"iso":"eng"}],"project":[{"_id":"267DFB90-B435-11E9-9278-68D0E5697425","name":"Plasticity in the cerebellum: Which molecular mechanisms are behind physiological learning?"}],"month":"04","publication_identifier":{"issn":["2663 - 337X"]},"author":[{"full_name":"Alcarva, Catarina","last_name":"Alcarva","first_name":"Catarina","id":"3A96634C-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-04-26T12:16:56Z","date_created":"2023-04-06T07:54:09Z","year":"2023","publication_status":"published","department":[{"_id":"GradSch"},{"_id":"RySh"}],"publisher":"Institute of Science and Technology Austria","file_date_updated":"2023-04-07T06:18:05Z"},{"month":"08","publication_identifier":{"eissn":["2041-1723"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"pmid":["37633939"]},"quality_controlled":"1","doi":"10.1038/s41467-023-40930-6","language":[{"iso":"eng"}],"article_number":"5231","file_date_updated":"2023-09-06T06:50:07Z","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.).","year":"2023","pmid":1,"publication_status":"published","department":[{"_id":"RySh"}],"publisher":"Springer Nature","author":[{"first_name":"Nicholas C.","last_name":"Vierra","full_name":"Vierra, Nicholas C."},{"full_name":"Ribeiro-Silva, Luisa","last_name":"Ribeiro-Silva","first_name":"Luisa"},{"first_name":"Michael","last_name":"Kirmiz","full_name":"Kirmiz, Michael"},{"full_name":"Van Der List, Deborah","last_name":"Van Der List","first_name":"Deborah"},{"full_name":"Bhandari, Pradeep","first_name":"Pradeep","last_name":"Bhandari","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481"},{"full_name":"Mack, Olivia A.","last_name":"Mack","first_name":"Olivia A."},{"full_name":"Carroll, James","last_name":"Carroll","first_name":"James"},{"full_name":"Le Monnier, Elodie","last_name":"Le Monnier","first_name":"Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sue A.","last_name":"Aicher","full_name":"Aicher, Sue A."},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Trimmer, James S.","last_name":"Trimmer","first_name":"James S."}],"date_updated":"2023-09-06T06:53:32Z","date_created":"2023-09-03T22:01:14Z","volume":14,"scopus_import":"1","day":"26","article_processing_charge":"Yes","has_accepted_license":"1","publication":"Nature Communications","citation":{"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).","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.","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","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.","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","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."},"article_type":"original","date_published":"2023-08-26T00:00:00Z","type":"journal_article","abstract":[{"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.","lang":"eng"}],"_id":"14253","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","title":"Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling","ddc":["570"],"intvolume":" 14","file":[{"file_name":"2023_NatureComm_Vierra.pdf","access_level":"open_access","file_size":9412549,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"14270","date_created":"2023-09-06T06:50:07Z","date_updated":"2023-09-06T06:50:07Z","checksum":"6ab8aab4e957f626a09a1c73db3388fb","success":1}],"oa_version":"Published Version"}]