--- _id: '12567' abstract: - lang: eng text: Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations. acknowledgement: This work has been supported by funding of the German Research Foundation (Deutsche Forschungsgemeinschaft [DFG], CRC 166, Project B06 to M.H. and A.-L.S., FOR 3004 SYNABS P1 to M.H.) and by the Interdisciplinary Clinical Research Center (IZKF) Würzburg (Z-3/69 to M.M.P., N-229 to M.H. and A.-L.S.). A.M. is funded by the University of Leipzig Clinician Scientist Program. article_number: '2128' article_processing_charge: No article_type: original author: - first_name: Achmed full_name: Mrestani, Achmed last_name: Mrestani - first_name: Katharina full_name: Lichter, Katharina id: 39302e62-fcfc-11ec-8196-8b01447dbd3d last_name: Lichter - first_name: Anna Leena full_name: Sirén, Anna Leena last_name: Sirén - first_name: Manfred full_name: Heckmann, Manfred last_name: Heckmann - first_name: Mila M. full_name: Paul, Mila M. last_name: Paul - first_name: Martin full_name: Pauli, Martin last_name: Pauli citation: ama: Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. 2023;24(3). doi:10.3390/ijms24032128 apa: Mrestani, A., Lichter, K., Sirén, A. L., Heckmann, M., Paul, M. M., & Pauli, M. (2023). Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms24032128 chicago: Mrestani, Achmed, Katharina Lichter, Anna Leena Sirén, Manfred Heckmann, Mila M. Paul, and Martin Pauli. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” International Journal of Molecular Sciences. MDPI, 2023. https://doi.org/10.3390/ijms24032128. ieee: A. Mrestani, K. Lichter, A. L. Sirén, M. Heckmann, M. M. Paul, and M. Pauli, “Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation,” International Journal of Molecular Sciences, vol. 24, no. 3. MDPI, 2023. ista: Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. 2023. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. 24(3), 2128. mla: Mrestani, Achmed, et al. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” International Journal of Molecular Sciences, vol. 24, no. 3, 2128, MDPI, 2023, doi:10.3390/ijms24032128. short: A. Mrestani, K. Lichter, A.L. Sirén, M. Heckmann, M.M. Paul, M. Pauli, International Journal of Molecular Sciences 24 (2023). date_created: 2023-02-19T23:00:56Z date_published: 2023-01-21T00:00:00Z date_updated: 2023-08-01T13:16:36Z day: '21' ddc: - '570' department: - _id: PeJo doi: 10.3390/ijms24032128 external_id: isi: - '000930324700001' file: - access_level: open_access checksum: 69a35dcd3e0249f902ab881b06ee2e58 content_type: application/pdf creator: dernst date_created: 2023-02-20T07:09:27Z date_updated: 2023-02-20T07:09:27Z file_id: '12569' file_name: 2023_IJMS_Mrestani.pdf file_size: 2823025 relation: main_file success: 1 file_date_updated: 2023-02-20T07:09:27Z has_accepted_license: '1' intvolume: ' 24' isi: 1 issue: '3' language: - iso: eng month: '01' oa: 1 oa_version: Published Version publication: International Journal of Molecular Sciences publication_identifier: eissn: - 1422-0067 publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation 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: 24 year: '2023' ... --- _id: '12759' abstract: - lang: eng text: Stereological methods for estimating the 3D particle size and density from 2D projections are essential to many research fields. These methods are, however, prone to errors arising from undetected particle profiles due to sectioning and limited resolution, known as ‘lost caps’. A potential solution developed by Keiding, Jensen, and Ranek in 1972, which we refer to as the Keiding model, accounts for lost caps by quantifying the smallest detectable profile in terms of its limiting ‘cap angle’ (ϕ), a size-independent measure of a particle’s distance from the section surface. However, this simple solution has not been widely adopted nor tested. Rather, model-independent design-based stereological methods, which do not explicitly account for lost caps, have come to the fore. Here, we provide the first experimental validation of the Keiding model by comparing the size and density of particles estimated from 2D projections with direct measurement from 3D EM reconstructions of the same tissue. We applied the Keiding model to estimate the size and density of somata, nuclei and vesicles in the cerebellum of mice and rats, where high packing density can be problematic for design-based methods. Our analysis reveals a Gaussian distribution for ϕ rather than a single value. Nevertheless, curve fits of the Keiding model to the 2D diameter distribution accurately estimate the mean ϕ and 3D diameter distribution. While systematic testing using simulations revealed an upper limit to determining ϕ, our analysis shows that estimated ϕ can be used to determine the 3D particle density from the 2D density under a wide range of conditions, and this method is potentially more accurate than minimum-size-based lost-cap corrections and disector methods. Our results show the Keiding model provides an efficient means of accurately estimating the size and density of particles from 2D projections even under conditions of a high density. acknowledged_ssus: - _id: EM-Fac acknowledgement: "We thank the IST Austria Electron Microscopy Facility for technical support, and Diccon Coyle, Andrea Lőrincz and Zoltan Nusser for their helpful comments and discussions.\r\nFunding for JSR and RAS was from the Wellcome Trust (203048; 224499; https://\r\nwellcome.org/). RAS is in receipt of a Wellcome Trust Principal Research Fellowship (224499).\r\nFunding for CBM and PJ was from Fond zur Förderung der Wissenschaftlichen Forschung (V\r\n739-B27 Elise-Richter Programme to CBM, Z 312-B27 Wittgenstein Award to PJ; \r\nhttps://www.fwf.ac.at). PJ received funding from the European Research Council (ERC; https://erc.europa.eu) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692). NH was supported by a European\r\nResearch Council Advanced Grant (ERC-AG787157)." article_number: e0277148 article_processing_charge: No article_type: original author: - first_name: Jason Seth full_name: Rothman, Jason Seth last_name: Rothman - 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: Noemi full_name: Holderith, Noemi last_name: Holderith - 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: R. full_name: Angus Silver, R. last_name: Angus Silver citation: ama: Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. 2023;18(3 March). doi:10.1371/journal.pone.0277148 apa: Rothman, J. S., Borges Merjane, C., Holderith, N., Jonas, P. M., & Angus Silver, R. (2023). Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. Public Library of Science. https://doi.org/10.1371/journal.pone.0277148 chicago: Rothman, Jason Seth, Carolina Borges Merjane, Noemi Holderith, Peter M Jonas, and R. Angus Silver. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE. Public Library of Science, 2023. https://doi.org/10.1371/journal.pone.0277148. ieee: J. S. Rothman, C. Borges Merjane, N. Holderith, P. M. Jonas, and R. Angus Silver, “Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy,” PLoS ONE, vol. 18, no. 3 March. Public Library of Science, 2023. ista: Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. 2023. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. 18(3 March), e0277148. mla: Rothman, Jason Seth, et al. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE, vol. 18, no. 3 March, e0277148, Public Library of Science, 2023, doi:10.1371/journal.pone.0277148. short: J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver, PLoS ONE 18 (2023). date_created: 2023-03-26T22:01:07Z date_published: 2023-03-17T00:00:00Z date_updated: 2023-08-01T13:46:39Z day: '17' ddc: - '570' department: - _id: PeJo doi: 10.1371/journal.pone.0277148 ec_funded: 1 external_id: isi: - '001024737400001' file: - access_level: open_access checksum: 2380331ec27cc87808826fc64419ac1c content_type: application/pdf creator: dernst date_created: 2023-03-27T06:51:09Z date_updated: 2023-03-27T06:51:09Z file_id: '12770' file_name: 2023_PLoSOne_Rothman.pdf file_size: 7290413 relation: main_file success: 1 file_date_updated: 2023-03-27T06:51:09Z has_accepted_license: '1' intvolume: ' 18' isi: 1 issue: 3 March language: - iso: eng month: '03' oa: 1 oa_version: Published Version 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: 2696E7FE-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: V00739 name: Structural plasticity at mossy fiber-CA3 synapses publication: PLoS ONE publication_identifier: eissn: - 1932-6203 publication_status: published publisher: Public Library of Science quality_controlled: '1' scopus_import: '1' status: public title: Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy 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: 18 year: '2023' ... --- _id: '12515' abstract: - lang: eng text: "Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents.\r\nMethods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques.\r\nResults: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity.\r\nDiscussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues." acknowledgement: This work was partially supported by a grant from “Consello Social Universidade de Santiago de Compostela” 2022-PU004.We would like to show special gratitude to Prof. Ludwig Wagner (Medical University, Vienna) for kindly providing us with the secretagogin antibody. We thank the Wildlife Recovery Centres of Galicia, Dirección Xeral de Patrimonio Natural (Xunta de Galicia, Spain), and Federación Galega de Caza for providing the red foxes used in this study. article_number: '1097467' article_processing_charge: No article_type: original author: - first_name: Irene full_name: Ortiz-Leal, Irene last_name: Ortiz-Leal - first_name: Mateo V. full_name: Torres, Mateo V. last_name: Torres - first_name: Victor M full_name: Vargas Barroso, Victor M id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87 last_name: Vargas Barroso - first_name: Luis Eusebio full_name: Fidalgo, Luis Eusebio last_name: Fidalgo - first_name: Ana María full_name: López-Beceiro, Ana María last_name: López-Beceiro - first_name: Jorge A. full_name: Larriva-Sahd, Jorge A. last_name: Larriva-Sahd - first_name: Pablo full_name: Sánchez-Quinteiro, Pablo last_name: Sánchez-Quinteiro citation: ama: Ortiz-Leal I, Torres MV, Vargas Barroso VM, et al. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. 2023;16. doi:10.3389/fnana.2022.1097467 apa: Ortiz-Leal, I., Torres, M. V., Vargas Barroso, V. M., Fidalgo, L. E., López-Beceiro, A. M., Larriva-Sahd, J. A., & Sánchez-Quinteiro, P. (2023). The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.1097467 chicago: Ortiz-Leal, Irene, Mateo V. Torres, Victor M Vargas Barroso, Luis Eusebio Fidalgo, Ana María López-Beceiro, Jorge A. Larriva-Sahd, and Pablo Sánchez-Quinteiro. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” Frontiers in Neuroanatomy. Frontiers, 2023. https://doi.org/10.3389/fnana.2022.1097467. ieee: I. Ortiz-Leal et al., “The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway,” Frontiers in Neuroanatomy, vol. 16. Frontiers, 2023. ista: Ortiz-Leal I, Torres MV, Vargas Barroso VM, Fidalgo LE, López-Beceiro AM, Larriva-Sahd JA, Sánchez-Quinteiro P. 2023. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. 16, 1097467. mla: Ortiz-Leal, Irene, et al. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” Frontiers in Neuroanatomy, vol. 16, 1097467, Frontiers, 2023, doi:10.3389/fnana.2022.1097467. short: I. Ortiz-Leal, M.V. Torres, V.M. Vargas Barroso, L.E. Fidalgo, A.M. López-Beceiro, J.A. Larriva-Sahd, P. Sánchez-Quinteiro, Frontiers in Neuroanatomy 16 (2023). date_created: 2023-02-05T23:01:00Z date_published: 2023-01-10T00:00:00Z date_updated: 2023-08-16T11:37:52Z day: '10' ddc: - '570' department: - _id: PeJo doi: 10.3389/fnana.2022.1097467 external_id: isi: - '000919786900001' pmid: - '36704406' file: - access_level: open_access checksum: 49cd40f3bda6f267079427042e7d15e3 content_type: application/pdf creator: dernst date_created: 2023-02-06T07:56:14Z date_updated: 2023-02-06T07:56:14Z file_id: '12518' file_name: 2022_FrontiersNeuroanatomy_OrtizLeal.pdf file_size: 21943473 relation: main_file success: 1 file_date_updated: 2023-02-06T07:56:14Z has_accepted_license: '1' intvolume: ' 16' isi: 1 language: - iso: eng month: '01' oa: 1 oa_version: Published Version pmid: 1 publication: Frontiers in Neuroanatomy publication_identifier: eissn: - 1662-5129 publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway 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: 16 year: '2023' ... --- _id: '12786' abstract: - lang: eng text: AMPA glutamate receptors (AMPARs) mediate excitatory neurotransmission throughout the brain. Their signalling is uniquely diversified by brain region-specific auxiliary subunits, providing an opportunity for the development of selective therapeutics. AMPARs associated with TARP γ8 are enriched in the hippocampus, and are targets of emerging anti-epileptic drugs. To understand their therapeutic activity, we determined cryo-EM structures of the GluA1/2-γ8 receptor associated with three potent, chemically diverse ligands. We find that despite sharing a lipid-exposed and water-accessible binding pocket, drug action is differentially affected by binding-site mutants. Together with patch-clamp recordings and MD simulations we also demonstrate that ligand-triggered reorganisation of the AMPAR-TARP interface contributes to modulation. Unexpectedly, one ligand (JNJ-61432059) acts bifunctionally, negatively affecting GluA1 but exerting positive modulatory action on GluA2-containing AMPARs, in a TARP stoichiometry-dependent manner. These results further illuminate the action of TARPs, demonstrate the sensitive balance between positive and negative modulatory action, and provide a mechanistic platform for development of both positive and negative selective AMPAR modulators. acknowledgement: We thank James Krieger for generating the ‘proDy’ interaction maps in Fig. 5B and S7C, and Jan-Niklas Dohrke for critically reading the manuscript. We thank members of the Greger lab for insightful comments during this study. We acknowledge Trevor Rutherford for confirming ligand integrity by NMR. We are also grateful to LMB scientific computing and the EM facility for their support. This research was funded in part by the Wellcome Trust (223194/Z/21/Z) to I.H.G. For the purpose of Open Access, the MRC Laboratory of Molecular Biology has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission. Further funding came from the Medical Research Council (MRU105174197) to I.H.G, and NIH grant (R56/R01MH123474) to T.N. article_number: '1659' article_processing_charge: No article_type: original author: - first_name: Danyang full_name: Zhang, Danyang last_name: Zhang - first_name: Remigijus full_name: Lape, Remigijus last_name: Lape - first_name: Saher A. full_name: Shaikh, Saher A. last_name: Shaikh - first_name: Bianka K. full_name: Kohegyi, Bianka K. last_name: Kohegyi - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Ondrej full_name: Cais, Ondrej last_name: Cais - first_name: Terunaga full_name: Nakagawa, Terunaga last_name: Nakagawa - first_name: Ingo H. full_name: Greger, Ingo H. last_name: Greger citation: ama: Zhang D, Lape R, Shaikh SA, et al. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. 2023;14. doi:10.1038/s41467-023-37259-5 apa: Zhang, D., Lape, R., Shaikh, S. A., Kohegyi, B. K., Watson, J., Cais, O., … Greger, I. H. (2023). Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-37259-5 chicago: Zhang, Danyang, Remigijus Lape, Saher A. Shaikh, Bianka K. Kohegyi, Jake Watson, Ondrej Cais, Terunaga Nakagawa, and Ingo H. Greger. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor Therapeutics.” Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-37259-5. ieee: D. Zhang et al., “Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics,” Nature Communications, vol. 14. Springer Nature, 2023. ista: Zhang D, Lape R, Shaikh SA, Kohegyi BK, Watson J, Cais O, Nakagawa T, Greger IH. 2023. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. 14, 1659. mla: Zhang, Danyang, et al. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor Therapeutics.” Nature Communications, vol. 14, 1659, Springer Nature, 2023, doi:10.1038/s41467-023-37259-5. short: D. Zhang, R. Lape, S.A. Shaikh, B.K. Kohegyi, J. Watson, O. Cais, T. Nakagawa, I.H. Greger, Nature Communications 14 (2023). date_created: 2023-04-02T22:01:09Z date_published: 2023-03-25T00:00:00Z date_updated: 2023-12-13T11:15:58Z day: '25' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41467-023-37259-5 external_id: isi: - '001066658700003' file: - access_level: open_access checksum: 0a97b31191432dae5853bbb5ccb7698d content_type: application/pdf creator: dernst date_created: 2023-04-03T06:38:56Z date_updated: 2023-04-03T06:38:56Z file_id: '12797' file_name: 2023_NatureComm_Zhang.pdf file_size: 2613996 relation: main_file success: 1 file_date_updated: 2023-04-03T06:38:56Z has_accepted_license: '1' intvolume: ' 14' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics 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: '13267' abstract: - lang: eng text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: E-Lib - _id: LifeSc - _id: M-Shop acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)." article_processing_charge: Yes article_type: original author: - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Eder full_name: Miguel Villalba, Eder id: 3FB91342-F248-11E8-B48F-1D18A9856A87 last_name: Miguel Villalba orcid: 0000-0001-5665-0430 - 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: Donglai full_name: Wei, Donglai last_name: Wei - first_name: Zudi full_name: Lin, Zudi last_name: Lin - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Jakob full_name: Troidl, Jakob last_name: Troidl - first_name: Johanna full_name: Beyer, Johanna last_name: Beyer - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon - 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: Wiebke full_name: Jahr, Wiebke id: 425C1CE8-F248-11E8-B48F-1D18A9856A87 last_name: Jahr - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Johannes full_name: Broichhagen, Johannes last_name: Broichhagen - first_name: Seth G.N. full_name: Grant, Seth G.N. last_name: Grant - 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: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Hanspeter full_name: Pfister, Hanspeter last_name: Pfister - first_name: Bernd full_name: Bickel, Bernd id: 49876194-F248-11E8-B48F-1D18A9856A87 last_name: Bickel orcid: 0000-0001-6511-9385 - 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: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6 apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6 chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6. ieee: P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023. ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265. mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6. short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265. date_created: 2023-07-23T22:01:13Z date_published: 2023-08-01T00:00:00Z date_updated: 2024-01-10T08:37:48Z day: '01' department: - _id: PeJo - _id: GaNo - _id: BeBi - _id: JoDa - _id: Bio doi: 10.1038/s41592-023-01936-6 ec_funded: 1 external_id: isi: - '001025621500001' pmid: - '37429995' intvolume: ' 20' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41592-023-01936-6 month: '08' oa: 1 oa_version: Published Version page: 1256-1265 pmid: 1 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: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 24F9549A-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715767' name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling' - _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: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry - _id: 2668BFA0-B435-11E9-9278-68D0E5697425 grant_number: LT00057 name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration publication: Nature Methods publication_identifier: eissn: - 1548-7105 issn: - 1548-7091 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/danzllab/LIONESS record: - id: '12817' relation: research_data status: public - id: '14770' relation: shorter_version status: public scopus_import: '1' status: public title: Dense 4D nanoscale reconstruction of living brain tissue type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 20 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: '10763' abstract: - lang: eng text: "AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory\r\nsynapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs)\r\nleads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission\r\nand are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs)\r\nthrough currently incompletely resolved mechanisms. Here, electron cryo-microscopy\r\nstructures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states\r\n(at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’),\r\nelucidating how this TARP stabilizes specific gating states. We further show how TARPs alter\r\nchannel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we\r\nreveal that the Q/R-editing site couples the channel constriction at the filter entrance to the\r\ngate, and forms the major cation binding site in the conduction path. Our results provide a\r\nmechanistic framework of how TARPs modulate AMPAR gating and conductance." acknowledgement: "We thank Ondrej Cais for critical reading of the manuscript. We are grateful to LMB\r\nscientific computing and the EM facility for support, Paul Emsley for help with model\r\nbuilding and Takanori Nakane for helpful comments with Relion 3.1. This work was\r\nsupported by grants from the Medical Research Council (MC_U105174197) and BBSRC\r\n(BB/N002113/1) to I.H.G, and grants from the MCIN/AEI/ 10.13039/501100011033 and\r\n“ESF Investing in your future” to B.H (PID2019-106284GA-I00 and RYC2018-025720-I)." article_number: '734' article_processing_charge: No article_type: original author: - first_name: Beatriz full_name: Herguedas, Beatriz last_name: Herguedas - first_name: Bianka K. full_name: Kohegyi, Bianka K. last_name: Kohegyi - first_name: Jan Niklas full_name: Dohrke, Jan Niklas last_name: Dohrke - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Danyang full_name: Zhang, Danyang last_name: Zhang - first_name: Hinze full_name: Ho, Hinze last_name: Ho - first_name: Saher A. full_name: Shaikh, Saher A. last_name: Shaikh - first_name: Remigijus full_name: Lape, Remigijus last_name: Lape - first_name: James M. full_name: Krieger, James M. last_name: Krieger - first_name: Ingo H. full_name: Greger, Ingo H. last_name: Greger citation: ama: Herguedas B, Kohegyi BK, Dohrke JN, et al. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 2022;13. doi:10.1038/s41467-022-28404-7 apa: Herguedas, B., Kohegyi, B. K., Dohrke, J. N., Watson, J., Zhang, D., Ho, H., … Greger, I. H. (2022). Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28404-7 chicago: Herguedas, Beatriz, Bianka K. Kohegyi, Jan Niklas Dohrke, Jake Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, and Ingo H. Greger. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28404-7. ieee: B. Herguedas et al., “Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor,” Nature Communications, vol. 13. Springer Nature, 2022. ista: Herguedas B, Kohegyi BK, Dohrke JN, Watson J, Zhang D, Ho H, Shaikh SA, Lape R, Krieger JM, Greger IH. 2022. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 13, 734. mla: Herguedas, Beatriz, et al. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” Nature Communications, vol. 13, 734, Springer Nature, 2022, doi:10.1038/s41467-022-28404-7. short: B. Herguedas, B.K. Kohegyi, J.N. Dohrke, J. Watson, D. Zhang, H. Ho, S.A. Shaikh, R. Lape, J.M. Krieger, I.H. Greger, Nature Communications 13 (2022). date_created: 2022-02-20T23:01:30Z date_published: 2022-02-08T00:00:00Z date_updated: 2023-08-02T14:25:33Z day: '08' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41467-022-28404-7 external_id: isi: - '000757297200008' pmid: - '35136046' file: - access_level: open_access checksum: d86ee8eabe8b794730729ffbb1a8832e content_type: application/pdf creator: dernst date_created: 2022-02-21T07:59:32Z date_updated: 2022-02-21T07:59:32Z file_id: '10778' file_name: 2022_NatureCommunications_Herguedas.pdf file_size: 2625540 relation: main_file success: 1 file_date_updated: 2022-02-21T07:59:32Z has_accepted_license: '1' intvolume: ' 13' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - '20411723' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor 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: 13 year: '2022' ... --- _id: '11951' abstract: - lang: eng text: The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain. acknowledged_ssus: - _id: Bio - _id: SSU acknowledgement: We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility of the Institute of Science and Technology Austria (ISTA) for image analysis scripts and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for help with single-unit clustering. Finally, we also thank B. Suter for discussions, A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service Units of ISTA for efficient support. This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.). article_number: '4826' article_processing_charge: No article_type: original author: - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon - first_name: Karola full_name: Käfer, Karola id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87 last_name: Käfer - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 - 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: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 2022;13. doi:10.1038/s41467-022-32559-8 apa: Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., & Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32559-8 chicago: Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32559-8. ieee: Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M. Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory,” Nature Communications, vol. 13. Springer Nature, 2022. ista: Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 13, 4826. mla: Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications, vol. 13, 4826, Springer Nature, 2022, doi:10.1038/s41467-022-32559-8. short: Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022). date_created: 2022-08-24T08:25:50Z date_published: 2022-08-16T00:00:00Z date_updated: 2023-08-03T13:01:19Z day: '16' ddc: - '570' department: - _id: JoCs - _id: PeJo - _id: JoDa doi: 10.1038/s41467-022-32559-8 ec_funded: 1 external_id: isi: - '000841396400008' file: - access_level: open_access checksum: 405936d9e4d33625d80c093c9713a91f content_type: application/pdf creator: dernst date_created: 2022-08-26T11:51:40Z date_updated: 2022-08-26T11:51:40Z file_id: '11990' file_name: 2022_NatureCommunications_BenSimon.pdf file_size: 5910357 relation: main_file success: 1 file_date_updated: 2022-08-26T11:51:40Z has_accepted_license: '1' intvolume: ' 13' isi: 1 keyword: - General Physics and Astronomy - General Biochemistry - Genetics and Molecular Biology - General Chemistry - Multidisciplinary language: - iso: eng month: '08' oa: 1 oa_version: Published Version 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: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' status: public title: A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory 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: 13 year: '2022' ... --- _id: '12288' abstract: - lang: eng text: To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo. acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS). article_number: '79848' article_processing_charge: No article_type: original author: - first_name: Anton L full_name: Sumser, Anton L id: 3320A096-F248-11E8-B48F-1D18A9856A87 last_name: Sumser orcid: 0000-0002-4792-1881 - 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: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon citation: ama: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 2022;11. doi:10.7554/elife.79848 apa: Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.79848 chicago: Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.79848. ieee: A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” eLife, vol. 11. eLife Sciences Publications, 2022. ista: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848. mla: Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848. short: A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022). date_created: 2023-01-16T10:04:15Z date_published: 2022-09-15T00:00:00Z date_updated: 2023-08-04T10:29:48Z day: '15' ddc: - '570' department: - _id: MaJö - _id: PeJo doi: 10.7554/elife.79848 ec_funded: 1 external_id: isi: - '000892204300001' pmid: - '36040301' file: - access_level: open_access checksum: 5a2a65e3e7225090c3d8199f3bbd7b7b content_type: application/pdf creator: dernst date_created: 2023-01-30T11:50:53Z date_updated: 2023-01-30T11:50:53Z file_id: '12463' file_name: 2022_eLife_Sumser.pdf file_size: 8506811 relation: main_file success: 1 file_date_updated: 2023-01-30T11:50:53Z has_accepted_license: '1' intvolume: ' 11' isi: 1 keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng month: '09' oa: 1 oa_version: Published Version 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: 2634E9D2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '756502' name: Circuits of Visual Attention - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 266D407A-B435-11E9-9278-68D0E5697425 grant_number: LT000256 name: Neuronal networks of salience and spatial detection in the murine superior colliculus - _id: 264FEA02-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1098-2017 name: Connecting sensory with motor processing in the superior colliculus publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde 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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2022' ... --- _id: '11196' abstract: - lang: eng text: "One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.\r\n" acknowledged_ssus: - _id: EM-Fac - _id: PreCl alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim citation: ama: Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. 2022. doi:10.15479/at:ista:11196 apa: Kim, O. (2022). Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11196 chicago: Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11196. ieee: O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022. ista: Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria. mla: Kim, Olena. Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11196. short: O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022. date_created: 2022-04-20T09:47:12Z date_published: 2022-04-20T00:00:00Z date_updated: 2023-08-18T06:31:52Z day: '20' ddc: - '570' degree_awarded: PhD department: - _id: PeJo - _id: GradSch doi: 10.15479/at:ista:11196 ec_funded: 1 file: - access_level: open_access checksum: 1616a8bf6f13a57c892dac873dcd0936 content_type: application/pdf creator: okim date_created: 2022-04-20T14:21:56Z date_updated: 2023-04-20T22:30:03Z embargo: 2023-04-19 file_id: '11220' file_name: Olena_KIM_thesis_final.pdf file_size: 21273537 relation: main_file - access_level: closed checksum: 1acb433f98dc42abb0b4b0cbb0c4b918 content_type: application/x-zip-compressed creator: okim date_created: 2022-04-20T14:22:56Z date_updated: 2023-04-20T22:30:03Z embargo_to: open_access file_id: '11221' file_name: KIM_thesis_final.zip file_size: 59248569 relation: source_file file_date_updated: 2023-04-20T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '132' project: - _id: 25BAF7B2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '708497' name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C3DBB6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01205 name: Zellkommunikation in Gesundheit und Krankheit - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '11222' relation: part_of_dissertation status: public - id: '7473' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses 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: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2022' ... --- _id: '11943' abstract: - lang: eng text: Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue. article_processing_charge: No author: - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Eder full_name: Miguel Villalba, Eder id: 3FB91342-F248-11E8-B48F-1D18A9856A87 last_name: Miguel Villalba orcid: 0000-0001-5665-0430 - 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: Donglai full_name: Wei, Donglai last_name: Wei - first_name: Zudi full_name: Lin, Zudi last_name: Lin - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Jakob full_name: Troidl, Jakob last_name: Troidl - first_name: Johanna full_name: Beyer, Johanna last_name: Beyer - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon - 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: Wiebke full_name: Jahr, Wiebke id: 425C1CE8-F248-11E8-B48F-1D18A9856A87 last_name: Jahr - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Johannes full_name: Broichhagen, Johannes last_name: Broichhagen - first_name: Seth G. N. full_name: Grant, Seth G. N. last_name: Grant - 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: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Hanspeter full_name: Pfister, Hanspeter last_name: Pfister - first_name: Bernd full_name: Bickel, Bernd id: 49876194-F248-11E8-B48F-1D18A9856A87 last_name: Bickel orcid: 0000-0001-6511-9385 - 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: Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431 apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431 chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431. ieee: P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory. ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431. mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431. short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.). date_created: 2022-08-23T11:07:59Z date_published: 2022-05-09T00:00:00Z date_updated: 2024-03-27T23:30:20Z day: '09' department: - _id: PeJo - _id: GaNo - _id: BeBi - _id: JoDa doi: 10.1101/2022.03.16.484431 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.03.16.484431 month: '05' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '12470' relation: dissertation_contains status: public status: public title: Saturated reconstruction of living brain tissue type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '11950' 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 nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons. article_processing_charge: No 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: 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: 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. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272 apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272 chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272. ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory. ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272. mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272. short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.). date_created: 2022-08-24T08:24:52Z date_published: 2022-08-18T00:00:00Z date_updated: 2024-03-27T23:30:20Z day: '18' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa doi: 10.1101/2022.08.17.504272 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.08.17.504272 month: '08' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '12470' relation: dissertation_contains status: public status: public title: Uncovering brain tissue architecture across scales with super-resolution light microscopy type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '9097' abstract: - lang: eng text: Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving TNFα, IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of TNFα, IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of TNFα would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis. acknowledgement: RP acknowledges the Department of Science and Technology, India for the support through the DST-INSPIRE Faculty Award (DST/INSPIRE/04/2015/001939). This work was supported by the Engineering and Physical Sciences Research Council (EPSRC), United Kingdom (Grant numbers EP/J018295/1, EP/J018392/1, EP/N014391/1). The contribution of RP was also supported by the later Grant. This work was generously supported by the Welcome Trust Institutional Strategic Support Award (204909/Z/16/Z) too. The contribution of MG was supported by the EPSRC via EP/N014391/1 and a Wellcome Trust Institutional Strategic Support Award (WT105618MA). The contribution of YA was generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA). article_number: '2204' article_processing_charge: No article_type: original author: - first_name: Rakesh full_name: Pandey, Rakesh last_name: Pandey - first_name: Yusur full_name: Al-Nuaimi, Yusur last_name: Al-Nuaimi - first_name: Rajiv Kumar full_name: Mishra, Rajiv Kumar id: 46CB58F2-F248-11E8-B48F-1D18A9856A87 last_name: Mishra - first_name: Sarah K. full_name: Spurgeon, Sarah K. last_name: Spurgeon - first_name: Marc full_name: Goodfellow, Marc last_name: Goodfellow citation: ama: Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 2021;11. doi:10.1038/s41598-020-80507-7 apa: Pandey, R., Al-Nuaimi, Y., Mishra, R. K., Spurgeon, S. K., & Goodfellow, M. (2021). Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. Springer Nature. https://doi.org/10.1038/s41598-020-80507-7 chicago: Pandey, Rakesh, Yusur Al-Nuaimi, Rajiv Kumar Mishra, Sarah K. Spurgeon, and Marc Goodfellow. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports. Springer Nature, 2021. https://doi.org/10.1038/s41598-020-80507-7. ieee: R. Pandey, Y. Al-Nuaimi, R. K. Mishra, S. K. Spurgeon, and M. Goodfellow, “Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis,” Scientific Reports, vol. 11. Springer Nature, 2021. ista: Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. 2021. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 11, 2204. mla: Pandey, Rakesh, et al. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports, vol. 11, 2204, Springer Nature, 2021, doi:10.1038/s41598-020-80507-7. short: R. Pandey, Y. Al-Nuaimi, R.K. Mishra, S.K. Spurgeon, M. Goodfellow, Scientific Reports 11 (2021). date_created: 2021-02-07T23:01:12Z date_published: 2021-01-26T00:00:00Z date_updated: 2022-08-19T07:22:23Z day: '26' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41598-020-80507-7 file: - access_level: open_access checksum: e8a68df48750712671f5c47b0228e531 content_type: application/pdf creator: dernst date_created: 2021-02-09T07:33:23Z date_updated: 2021-02-09T07:33:23Z file_id: '9106' file_name: 2021_ScientificReports_Pandey.pdf file_size: 2885056 relation: main_file success: 1 file_date_updated: 2021-02-09T07:33:23Z has_accepted_license: '1' intvolume: ' 11' language: - iso: eng month: '01' oa: 1 oa_version: Published Version publication: Scientific Reports publication_identifier: eissn: - '20452322' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis 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: 11 year: '2021' ... --- _id: '9329' abstract: - lang: eng text: "Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.\r\nNew method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.\r\nResults: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.\r\nComparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.\r\nConclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity." acknowledged_ssus: - _id: SSU acknowledgement: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J.). We thank Drs. Jozsef Csicsvari, Christoph Lampert, and Federico Stella for critically reading previous manuscript versions. We are also grateful to Drs. Josh Merel and Ben Shababo for their help with applying the Bayesian detection method to our data. We also thank Florian Marr for technical assistance, Eleftheria Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for efficient support. article_number: '109125' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - 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: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 2021;357(6). doi:10.1016/j.jneumeth.2021.109125' apa: 'Zhang, X., Schlögl, A., Vandael, D. H., & Jonas, P. M. (2021). MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. Elsevier. https://doi.org/10.1016/j.jneumeth.2021.109125' chicago: 'Zhang, Xiaomin, Alois Schlögl, David H Vandael, and Peter M Jonas. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods. Elsevier, 2021. https://doi.org/10.1016/j.jneumeth.2021.109125.' ieee: 'X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo,” Journal of Neuroscience Methods, vol. 357, no. 6. Elsevier, 2021.' ista: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. 2021. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 357(6), 109125.' mla: 'Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods, vol. 357, no. 6, 109125, Elsevier, 2021, doi:10.1016/j.jneumeth.2021.109125.' short: X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021). date_created: 2021-04-18T22:01:39Z date_published: 2021-03-09T00:00:00Z date_updated: 2023-08-07T14:36:14Z day: '09' ddc: - '570' department: - _id: PeJo - _id: ScienComp doi: 10.1016/j.jneumeth.2021.109125 ec_funded: 1 external_id: isi: - '000661088500005' file: - access_level: open_access checksum: 2a5800d91b96d08b525e17319dcd5e44 content_type: application/pdf creator: dernst date_created: 2021-04-19T08:30:22Z date_updated: 2021-04-19T08:30:22Z file_id: '9339' file_name: 2021_JourNeuroscienceMeth_Zhang.pdf file_size: 6924738 relation: main_file success: 1 file_date_updated: 2021-04-19T08:30:22Z has_accepted_license: '1' intvolume: ' 357' isi: 1 issue: '6' language: - iso: eng month: '03' oa: 1 oa_version: Published Version 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 publication: Journal of Neuroscience Methods publication_identifier: eissn: - 1872-678X issn: - 0165-0270 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo' 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: 357 year: '2021' ... --- _id: '9549' abstract: - lang: eng text: 'AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. ' acknowledgement: We thank members of the Greger laboratory, B. Herguedas, J. Krieger and J.-N. Dohrke for comments on the manuscript; J. Krieger and J.-N. Dohrke for discussion, J. Krieger for help with the normal mode analysis, B. Köhegyi for help with cryo-EM imaging, V. Chang and K. Suzuki for helping to generate the CNIH2-1D4-HA stable cell line, M. Carvalho for assistance at early stages of this project, the LMB scientific computing and the cryo-EM facility for support, P. Emsley for help with model building, T. Nakane for helpful comments with RELION 3.1 and R. Warshamanage for helping with EMDA cryo-EM-map processing. We acknowledge the Diamond Light Source for access and support of the Cryo-EM facilities at the UK national electron bio10 imaging centre (eBIC), proposal EM17434, funded by the Wellcome Trust, MRC and BBSRC. This work was supported by grants from the Medical Research Council, as part of United Kingdom Research and Innovation (also known as UK Research and Innovation) (MC_U105174197) and BBSRC (BB/N002113/1) to I.H.G. article_processing_charge: No article_type: original author: - first_name: Danyang full_name: Zhang, Danyang last_name: Zhang - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Peter M. full_name: Matthews, Peter M. last_name: Matthews - first_name: Ondrej full_name: Cais, Ondrej last_name: Cais - first_name: Ingo H. full_name: Greger, Ingo H. last_name: Greger citation: ama: Zhang D, Watson J, Matthews PM, Cais O, Greger IH. Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. 2021;594:454-458. doi:10.1038/s41586-021-03613-0 apa: Zhang, D., Watson, J., Matthews, P. M., Cais, O., & Greger, I. H. (2021). Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. Springer Nature. https://doi.org/10.1038/s41586-021-03613-0 chicago: Zhang, Danyang, Jake Watson, Peter M. Matthews, Ondrej Cais, and Ingo H. Greger. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate Receptor.” Nature. Springer Nature, 2021. https://doi.org/10.1038/s41586-021-03613-0. ieee: D. Zhang, J. Watson, P. M. Matthews, O. Cais, and I. H. Greger, “Gating and modulation of a hetero-octameric AMPA glutamate receptor,” Nature, vol. 594. Springer Nature, pp. 454–458, 2021. ista: Zhang D, Watson J, Matthews PM, Cais O, Greger IH. 2021. Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. 594, 454–458. mla: Zhang, Danyang, et al. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate Receptor.” Nature, vol. 594, Springer Nature, 2021, pp. 454–58, doi:10.1038/s41586-021-03613-0. short: D. Zhang, J. Watson, P.M. Matthews, O. Cais, I.H. Greger, Nature 594 (2021) 454–458. date_created: 2021-06-13T22:01:33Z date_published: 2021-06-02T00:00:00Z date_updated: 2023-08-08T13:59:51Z day: '02' department: - _id: PeJo doi: 10.1038/s41586-021-03613-0 external_id: isi: - '000657238100003' pmid: - '34079129' intvolume: ' 594' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41586-021-03613-0 month: '06' oa: 1 oa_version: Published Version page: 454-458 pmid: 1 publication: Nature publication_identifier: eissn: - 1476-4687 issn: - 0028-0836 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Gating and modulation of a hetero-octameric AMPA glutamate receptor type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 594 year: '2021' ... --- _id: '9778' abstract: - lang: eng text: The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses. acknowledged_ssus: - _id: SSU acknowledgement: We thank Drs. Carolina Borges-Merjane and Jose Guzman for critically reading the manuscript, and Pablo Castillo for discussions. We are grateful to Alois Schlögl for help with analysis, Florian Marr for excellent technical assistance and cell reconstruction, Christina Altmutter for technical help, Eleftheria Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for support. This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award), both to P.J. article_number: '2912' article_processing_charge: No article_type: original author: - 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: Yuji full_name: Okamoto, Yuji id: 3337E116-F248-11E8-B48F-1D18A9856A87 last_name: Okamoto orcid: 0000-0003-0408-6094 - 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: Vandael DH, Okamoto Y, Jonas PM. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23153-5 apa: Vandael, D. H., Okamoto, Y., & Jonas, P. M. (2021). Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. Springer. https://doi.org/10.1038/s41467-021-23153-5 chicago: Vandael, David H, Yuji Okamoto, and Peter M Jonas. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” Nature Communications. Springer, 2021. https://doi.org/10.1038/s41467-021-23153-5. ieee: D. H. Vandael, Y. Okamoto, and P. M. Jonas, “Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses,” Nature Communications, vol. 12, no. 1. Springer, 2021. ista: Vandael DH, Okamoto Y, Jonas PM. 2021. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. 12(1), 2912. mla: Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” Nature Communications, vol. 12, no. 1, 2912, Springer, 2021, doi:10.1038/s41467-021-23153-5. short: D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021). date_created: 2021-08-06T07:22:55Z date_published: 2021-05-18T00:00:00Z date_updated: 2023-08-10T14:16:16Z day: '18' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41467-021-23153-5 ec_funded: 1 external_id: isi: - '000655481800014' file: - access_level: open_access checksum: 6036a8cdae95e1707c2a04d54e325ff4 content_type: application/pdf creator: kschuh date_created: 2021-12-17T11:34:50Z date_updated: 2021-12-17T11:34:50Z file_id: '10563' file_name: 2021_NatureCommunications_Vandael.pdf file_size: 3108845 relation: main_file success: 1 file_date_updated: 2021-12-17T11:34:50Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '1' keyword: - general physics and astronomy - general biochemistry - genetics and molecular biology - general chemistry language: - iso: eng month: '05' oa: 1 oa_version: Published Version 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 publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/ scopus_import: '1' status: public title: Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber 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: 12 year: '2021' ... --- _id: '9985' abstract: - lang: eng text: AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is therefore tightly controlled. Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but with limited coherence or comparison between reports, our understanding of this process is unclear. Here, combining synaptic recordings from mouse hippocampal slices and super-resolution imaging in dissociated cultures, we compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses. We show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission. Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density, where the NTD further tunes their positioning. This interplay between cytosolic (TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate synaptic transmission and plasticity. acknowledgement: The authors are very grateful to Andrew Penn for advice and discussions on surface receptor labelling in slice tissue, dissociated culture transfection, and for providing tdTomato and BirAER expression plasmids. This work would not have been possible without support from the Biological Services teams at both the Laboratory of Molecular Biology and Ares facilities. We are also very grateful to Nick Barry and Jerome Boulanger of the LMB Light Microscopy facility for support with confocal and STORM imaging and analysis, Junichi Takagi for providing scFv-Clasp expression constructs, Veronica Chang for assistance with scFv-Clasp protein production, and Nejc Kejzar for assistance with cluster analysis. We would like to thank Teru Nakagawa and Ole Paulsen for critical reading of the manuscript and constructive feedback. This work was supported by grants from the Medical Research Council (MC_U105174197) and BBSRC (BB/N002113/1). article_number: '5083' article_processing_charge: Yes article_type: original author: - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alexandra full_name: Pinggera, Alexandra last_name: Pinggera - first_name: Hinze full_name: Ho, Hinze last_name: Ho - first_name: Ingo H. full_name: Greger, Ingo H. last_name: Greger citation: ama: Watson J, Pinggera A, Ho H, Greger IH. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-25281-4 apa: Watson, J., Pinggera, A., Ho, H., & Greger, I. H. (2021). AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-021-25281-4 chicago: Watson, Jake, Alexandra Pinggera, Hinze Ho, and Ingo H. Greger. “AMPA Receptor Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications. Nature Publishing Group, 2021. https://doi.org/10.1038/s41467-021-25281-4. ieee: J. Watson, A. Pinggera, H. Ho, and I. H. Greger, “AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions,” Nature Communications, vol. 12, no. 1. Nature Publishing Group, 2021. ista: Watson J, Pinggera A, Ho H, Greger IH. 2021. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 12(1), 5083. mla: Watson, Jake, et al. “AMPA Receptor Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications, vol. 12, no. 1, 5083, Nature Publishing Group, 2021, doi:10.1038/s41467-021-25281-4. short: J. Watson, A. Pinggera, H. Ho, I.H. Greger, Nature Communications 12 (2021). date_created: 2021-09-05T22:01:23Z date_published: 2021-08-23T00:00:00Z date_updated: 2023-08-11T11:07:51Z day: '23' ddc: - '612' department: - _id: PeJo doi: 10.1038/s41467-021-25281-4 external_id: isi: - '000687672000006' pmid: - '34426577 ' file: - access_level: open_access checksum: 1bf4f6a561f96bc426d754de9cb57710 content_type: application/pdf creator: cchlebak date_created: 2021-09-08T12:57:06Z date_updated: 2021-09-08T12:57:06Z file_id: '9991' file_name: 2021_NatureCommunications_Watson.pdf file_size: 18310502 relation: main_file success: 1 file_date_updated: 2021-09-08T12:57:06Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '1' 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: Nature Publishing Group quality_controlled: '1' scopus_import: '1' status: public title: AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions 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: 12 year: '2021' ... --- _id: '9438' abstract: - lang: eng text: Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system. acknowledged_ssus: - _id: M-Shop acknowledgement: This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction, E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria, especially T. Asenov and Miba machine shop, for maximally efficient support. article_processing_charge: No article_type: original author: - 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: Yuji full_name: Okamoto, Yuji id: 3337E116-F248-11E8-B48F-1D18A9856A87 last_name: Okamoto orcid: 0000-0003-0408-6094 - 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: Victor M full_name: Vargas Barroso, Victor M id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87 last_name: Vargas Barroso - first_name: Benjamin full_name: Suter, Benjamin id: 4952F31E-F248-11E8-B48F-1D18A9856A87 last_name: Suter orcid: 0000-0002-9885-6936 - 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: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. 2021;16(6):2947–2967. doi:10.1038/s41596-021-00526-0 apa: Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter, B., & Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. Springer Nature. https://doi.org/10.1038/s41596-021-00526-0 chicago: Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” Nature Protocols. Springer Nature, 2021. https://doi.org/10.1038/s41596-021-00526-0. ieee: D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter, and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses,” Nature Protocols, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021. ista: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. 16(6), 2947–2967. mla: Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” Nature Protocols, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967, doi:10.1038/s41596-021-00526-0. short: D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967. date_created: 2021-05-30T22:01:24Z date_published: 2021-06-01T00:00:00Z date_updated: 2023-08-10T22:30:51Z day: '01' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41596-021-00526-0 ec_funded: 1 external_id: isi: - '000650528700003' pmid: - '33990799' file: - access_level: open_access checksum: 7eb580abd8893cdb0b410cf41bc8c263 content_type: application/pdf creator: cziletti date_created: 2021-07-08T12:27:55Z date_updated: 2021-12-02T23:30:05Z embargo: 2021-12-01 file_id: '9639' file_name: VandaeletalAuthorVersion2021.pdf file_size: 38574802 relation: main_file file_date_updated: 2021-12-02T23:30:05Z has_accepted_license: '1' intvolume: ' 16' isi: 1 issue: '6' language: - iso: eng month: '06' oa: 1 oa_version: Submitted Version page: 2947–2967 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: 2696E7FE-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: V00739 name: Structural plasticity at mossy fiber-CA3 synapses publication: Nature Protocols publication_identifier: eissn: - '17502799' issn: - '17542189' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 16 year: '2021' ... --- _id: '10816' abstract: - lang: eng text: Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks. acknowledged_ssus: - _id: SSU acknowledgement: We thank A. Aertsen, N. Kopell, W. Maass, A. Roth, F. Stella and T. Vogels for critically reading earlier versions of the manuscript. We are grateful to F. Marr and C. Altmutter for excellent technical assistance, E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for efficient support. Finally, we thank T. Carnevale, L. Erdös, M. Hines, D. Nykamp and D. Schröder for useful discussions, and R. Friedrich and S. Wiechert for sharing unpublished data. This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J. and P 31815 to S.J.G.). article_processing_charge: No article_type: original author: - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán orcid: 0000-0003-2209-5242 - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Benjamin full_name: Suter, Benjamin id: 4952F31E-F248-11E8-B48F-1D18A9856A87 last_name: Suter orcid: 0000-0002-9885-6936 - 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: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. 2021;1(12):830-842. doi:10.1038/s43588-021-00157-1 apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., & Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. Springer Nature. https://doi.org/10.1038/s43588-021-00157-1 chicago: Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang, Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” Nature Computational Science. Springer Nature, 2021. https://doi.org/10.1038/s43588-021-00157-1. ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M. Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network,” Nature Computational Science, vol. 1, no. 12. Springer Nature, pp. 830–842, 2021. ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. 1(12), 830–842. mla: Guzmán, José, et al. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” Nature Computational Science, vol. 1, no. 12, Springer Nature, 2021, pp. 830–42, doi:10.1038/s43588-021-00157-1. short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, Nature Computational Science 1 (2021) 830–842. date_created: 2022-03-04T08:32:36Z date_published: 2021-12-16T00:00:00Z date_updated: 2023-08-10T22:30:10Z day: '16' ddc: - '610' department: - _id: PeJo doi: 10.1038/s43588-021-00157-1 ec_funded: 1 file: - access_level: open_access checksum: 9fec5b667909ef52be96d502e4f8c2ae content_type: application/pdf creator: patrickd date_created: 2022-06-02T12:51:07Z date_updated: 2022-06-18T22:30:03Z embargo: 2022-06-17 file_id: '11430' file_name: Guzmanetal2021.pdf file_size: 1699466 relation: main_file - access_level: open_access checksum: 52a005b13a114e3c3a28fa6bbe8b1a8d content_type: application/pdf creator: patrickd date_created: 2022-06-02T12:53:47Z date_updated: 2022-06-18T22:30:03Z embargo: 2022-06-17 file_id: '11431' file_name: Guzmanetal2021Suppl.pdf file_size: 3005651 relation: supplementary_material title: Supplementary Material file_date_updated: 2022-06-18T22:30:03Z has_accepted_license: '1' intvolume: ' 1' issue: '12' keyword: - general medicine language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/647800 month: '12' oa: 1 oa_version: Submitted Version page: 830-842 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 publication: Nature Computational Science publication_identifier: issn: - 2662-8457 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: press_release url: https://ista.ac.at/en/news/spot-the-difference/ record: - id: '10110' relation: software status: public scopus_import: '1' status: public title: How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1 year: '2021' ... --- _id: '10110' abstract: - lang: eng text: Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks. author: - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán orcid: 0000-0003-2209-5242 - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Benjamin full_name: Suter, Benjamin id: 4952F31E-F248-11E8-B48F-1D18A9856A87 last_name: Suter orcid: 0000-0002-9885-6936 - 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: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. 2021. doi:10.15479/AT:ISTA:10110 apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., & Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. IST Austria. https://doi.org/10.15479/AT:ISTA:10110 chicago: Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang, Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” IST Austria, 2021. https://doi.org/10.15479/AT:ISTA:10110. ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M. Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.” IST Austria, 2021. ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network, IST Austria, 10.15479/AT:ISTA:10110. mla: Guzmán, José, et al. How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network. IST Austria, 2021, doi:10.15479/AT:ISTA:10110. short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, (2021). date_created: 2021-10-08T06:44:22Z date_published: 2021-12-16T00:00:00Z date_updated: 2024-03-27T23:30:11Z day: '16' ddc: - '005' department: - _id: PeJo - _id: ScienComp doi: 10.15479/AT:ISTA:10110 file: - access_level: open_access checksum: f92f8931cad0aa7e411c1715337bf408 content_type: application/x-zip-compressed creator: cchlebak date_created: 2021-10-08T08:46:04Z date_updated: 2021-10-08T08:46:04Z file_id: '10114' file_name: patternseparation-main (1).zip file_size: 332990101 relation: main_file success: 1 file_date_updated: 2021-10-08T08:46:04Z has_accepted_license: '1' license: https://opensource.org/licenses/GPL-3.0 month: '12' oa: 1 publisher: IST Austria related_material: link: - description: News on IST Webpage relation: press_release url: https://ist.ac.at/en/news/spot-the-difference/ record: - id: '10816' relation: used_for_analysis_in status: public status: public title: How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network tmp: legal_code_url: https://www.gnu.org/licenses/gpl-3.0.en.html name: GNU General Public License 3.0 short: GPL 3.0 type: software user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 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: '8001' abstract: - lang: eng text: Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network. acknowledged_ssus: - _id: SSU acknowledgement: This project received funding from the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Program (grant agreement 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung ( Z 312-B27 , Wittgenstein award to P.J. and V 739-B27 to C.B.-M.). We thank Drs. Jozsef Csicsvari, Jose Guzman, Erwin Neher, and Ryuichi Shigemoto for commenting on earlier versions of the manuscript. We are grateful to Walter Kaufmann, Daniel Gütl, and Vanessa Zheden for EM training; Alois Schlögl for programming; Florian Marr for excellent technical assistance and cell reconstruction; Christina Altmutter for technical help; Eleftheria Kralli-Beller for manuscript editing; Taija Makinen for providing the Prox1-CreERT2 mouse line; and the Scientific Service Units of IST Austria for support. article_processing_charge: No article_type: original author: - 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: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - 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: Vandael DH, Borges Merjane C, Zhang X, Jonas PM. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. 2020;107(3):509-521. doi:10.1016/j.neuron.2020.05.013 apa: Vandael, D. H., Borges Merjane, C., Zhang, X., & Jonas, P. M. (2020). Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.05.013 chicago: Vandael, David H, Carolina Borges Merjane, Xiaomin Zhang, and Peter M Jonas. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.05.013. ieee: D. H. Vandael, C. Borges Merjane, X. Zhang, and P. M. Jonas, “Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation,” Neuron, vol. 107, no. 3. Elsevier, pp. 509–521, 2020. ista: Vandael DH, Borges Merjane C, Zhang X, Jonas PM. 2020. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. 107(3), 509–521. mla: Vandael, David H., et al. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” Neuron, vol. 107, no. 3, Elsevier, 2020, pp. 509–21, doi:10.1016/j.neuron.2020.05.013. short: D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020) 509–521. date_created: 2020-06-22T13:29:05Z date_published: 2020-08-05T00:00:00Z date_updated: 2023-08-22T07:45:25Z day: '05' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.neuron.2020.05.013 ec_funded: 1 external_id: isi: - '000556135600004' pmid: - '32492366' file: - access_level: open_access checksum: 4030b2be0c9625d54694a1e9fb00305e content_type: application/pdf creator: dernst date_created: 2020-11-25T11:23:02Z date_updated: 2020-11-25T11:23:02Z file_id: '8811' file_name: 2020_Neuron_Vandael.pdf file_size: 4390833 relation: main_file success: 1 file_date_updated: 2020-11-25T11:23:02Z has_accepted_license: '1' intvolume: ' 107' isi: 1 issue: '3' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: 509-521 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: 2696E7FE-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: V00739 name: Structural plasticity at mossy fiber-CA3 synapses publication: Neuron publication_identifier: eissn: - '10974199' issn: - 0896-6273 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/possible-physical-trace-of-short-term-memory-found/ scopus_import: '1' status: public title: Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram 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: 107 year: '2020' ... --- _id: '8261' abstract: - lang: eng text: Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion. acknowledged_ssus: - _id: M-Shop - _id: ScienComp - _id: PreCl acknowledgement: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari, Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp recording. We are grateful to Florian Marr for cell labeling, cell reconstruction, and technical assistance; Ben Suter for helpful discussions; Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor Asenov (Machine Shop) for device construction. We also thank the Scientific Service Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical Facility) for efficient support. article_processing_charge: No article_type: original author: - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - 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: Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. 2020;107(6):1212-1225. doi:10.1016/j.neuron.2020.07.006 apa: Zhang, X., Schlögl, A., & Jonas, P. M. (2020). Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.07.006 chicago: Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.07.006. ieee: X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information flow from input to output in hippocampal granule cells,” Neuron, vol. 107, no. 6. Elsevier, pp. 1212–1225, 2020. ista: Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. 107(6), 1212–1225. mla: Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” Neuron, vol. 107, no. 6, Elsevier, 2020, pp. 1212–25, doi:10.1016/j.neuron.2020.07.006. short: X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225. date_created: 2020-08-14T09:36:05Z date_published: 2020-09-23T00:00:00Z date_updated: 2023-08-22T08:30:55Z day: '23' ddc: - '570' department: - _id: PeJo - _id: ScienComp doi: 10.1016/j.neuron.2020.07.006 ec_funded: 1 external_id: isi: - '000579698700009' pmid: - '32763145' file: - access_level: open_access checksum: 44a5960fc083a4cb3488d22224859fdc content_type: application/pdf creator: dernst date_created: 2020-12-04T09:29:21Z date_updated: 2020-12-04T09:29:21Z file_id: '8920' file_name: 2020_Neuron_Zhang.pdf file_size: 3011120 relation: main_file success: 1 file_date_updated: 2020-12-04T09:29:21Z has_accepted_license: '1' intvolume: ' 107' isi: 1 issue: '6' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: 1212-1225 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 publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Website relation: press_release url: https://ist.ac.at/en/news/the-bouncer-in-the-brain/ status: public title: Selective routing of spatial information flow from input to output in hippocampal granule cells 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: 107 year: '2020' ... --- _id: '7473' abstract: - lang: eng text: How structural and functional properties of synapses relate to each other is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms of synaptic transmission, and electron microscopy (EM) has provided insight into morphological properties of synapses. Here we describe an enhanced method for functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure freezing. We demonstrate that the improved method can be applied to intact networks in acute brain slices and organotypic slice cultures from mice. As a proof of concept, we probed vesicle pool changes during synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked vesicle pool and the functionally defined readily releasable pool and provide evidence of fast endocytosis at this synapse. Functional EM with acute slices and slice cultures has the potential to reveal the structural and functional mechanisms of transmission in intact, genetically perturbed, and disease-affected synapses. acknowledgement: 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. 692692 and Marie Sklodowska-Curie 708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27 Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa Zheden for extensive EM training, advice, and experimental assistance; Benjamin Suter for substantial help with light stimulation, ImageJ plugins for analysis, and manuscript editing; Florian Marr and Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing the Prox1-CreERT2 mouse line. article_processing_charge: No article_type: original author: - 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: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim - 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: Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 2020;105:992-1006. doi:10.1016/j.neuron.2019.12.022 apa: Borges Merjane, C., Kim, O., & Jonas, P. M. (2020). Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.12.022 chicago: Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2019.12.022. ieee: C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” Neuron, vol. 105. Elsevier, pp. 992–1006, 2020. ista: Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105, 992–1006. mla: Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron, vol. 105, Elsevier, 2020, pp. 992–1006, doi:10.1016/j.neuron.2019.12.022. short: C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006. date_created: 2020-02-10T15:59:45Z date_published: 2020-03-18T00:00:00Z date_updated: 2024-03-27T23:30:07Z day: '18' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.neuron.2019.12.022 ec_funded: 1 external_id: isi: - '000520854700008' pmid: - '31928842' file: - access_level: open_access checksum: 3582664addf26859e86ac5bec3e01416 content_type: application/pdf creator: dernst date_created: 2020-11-20T08:58:53Z date_updated: 2020-11-20T08:58:53Z file_id: '8778' file_name: 2020_Neuron_BorgesMerjane.pdf file_size: 9712957 relation: main_file success: 1 file_date_updated: 2020-11-20T08:58:53Z has_accepted_license: '1' intvolume: ' 105' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 992-1006 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: 25BAF7B2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '708497' name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 25C3DBB6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01205 name: Zellkommunikation in Gesundheit und Krankheit publication: Neuron publication_identifier: issn: - 0896-6273 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/flash-and-freeze-reveals-dynamics-of-nerve-connections/ record: - id: '11196' relation: dissertation_contains status: public scopus_import: '1' status: public title: Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices 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: 105 year: '2020' ... --- _id: '7405' abstract: - lang: eng text: Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, for example connectivity rules, to create millions of cell-to-cell connections. NetPyNE then enables users to generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis – connectivity matrices, voltage traces, spike raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing standardized formats (NeuroML and SONATA). NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate brain regions and phenomena. article_number: e44494 article_processing_charge: No article_type: original author: - first_name: Salvador full_name: Dura-Bernal, Salvador last_name: Dura-Bernal - first_name: Benjamin full_name: Suter, Benjamin id: 4952F31E-F248-11E8-B48F-1D18A9856A87 last_name: Suter orcid: 0000-0002-9885-6936 - first_name: Padraig full_name: Gleeson, Padraig last_name: Gleeson - first_name: Matteo full_name: Cantarelli, Matteo last_name: Cantarelli - first_name: Adrian full_name: Quintana, Adrian last_name: Quintana - first_name: Facundo full_name: Rodriguez, Facundo last_name: Rodriguez - first_name: David J full_name: Kedziora, David J last_name: Kedziora - first_name: George L full_name: Chadderdon, George L last_name: Chadderdon - first_name: Cliff C full_name: Kerr, Cliff C last_name: Kerr - first_name: Samuel A full_name: Neymotin, Samuel A last_name: Neymotin - first_name: Robert A full_name: McDougal, Robert A last_name: McDougal - first_name: Michael full_name: Hines, Michael last_name: Hines - first_name: Gordon MG full_name: Shepherd, Gordon MG last_name: Shepherd - first_name: William W full_name: Lytton, William W last_name: Lytton citation: ama: Dura-Bernal S, Suter B, Gleeson P, et al. NetPyNE, a tool for data-driven multiscale modeling of brain circuits. eLife. 2019;8. doi:10.7554/elife.44494 apa: Dura-Bernal, S., Suter, B., Gleeson, P., Cantarelli, M., Quintana, A., Rodriguez, F., … Lytton, W. W. (2019). NetPyNE, a tool for data-driven multiscale modeling of brain circuits. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.44494 chicago: Dura-Bernal, Salvador, Benjamin Suter, Padraig Gleeson, Matteo Cantarelli, Adrian Quintana, Facundo Rodriguez, David J Kedziora, et al. “NetPyNE, a Tool for Data-Driven Multiscale Modeling of Brain Circuits.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.44494. ieee: S. Dura-Bernal et al., “NetPyNE, a tool for data-driven multiscale modeling of brain circuits,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Dura-Bernal S, Suter B, Gleeson P, Cantarelli M, Quintana A, Rodriguez F, Kedziora DJ, Chadderdon GL, Kerr CC, Neymotin SA, McDougal RA, Hines M, Shepherd GM, Lytton WW. 2019. NetPyNE, a tool for data-driven multiscale modeling of brain circuits. eLife. 8, e44494. mla: Dura-Bernal, Salvador, et al. “NetPyNE, a Tool for Data-Driven Multiscale Modeling of Brain Circuits.” ELife, vol. 8, e44494, eLife Sciences Publications, 2019, doi:10.7554/elife.44494. short: S. Dura-Bernal, B. Suter, P. Gleeson, M. Cantarelli, A. Quintana, F. Rodriguez, D.J. Kedziora, G.L. Chadderdon, C.C. Kerr, S.A. Neymotin, R.A. McDougal, M. Hines, G.M. Shepherd, W.W. Lytton, ELife 8 (2019). date_created: 2020-01-30T09:08:01Z date_published: 2019-05-31T00:00:00Z date_updated: 2023-09-07T14:27:52Z day: '31' ddc: - '570' department: - _id: PeJo doi: 10.7554/elife.44494 external_id: isi: - '000468968400001' pmid: - '31025934' file: - access_level: open_access checksum: 7014189c11c10a12feeeae37f054871d content_type: application/pdf creator: dernst date_created: 2020-02-04T08:41:47Z date_updated: 2020-07-14T12:47:57Z file_id: '7444' file_name: 2019_eLife_DuraBernal.pdf file_size: 6182359 relation: main_file file_date_updated: 2020-07-14T12:47:57Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: NetPyNE, a tool for data-driven multiscale modeling of brain circuits 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: 8 year: '2019' ... --- _id: '11222' acknowledgement: This work was supported by the ERC and EU Horizon 2020 (ERC 692692; MSC-IF 708497) and FWF Z 312-B27 Wittgenstein award; W 1205-B09). article_number: A3.27 article_processing_charge: No author: - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim - 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: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: 'Kim O, Borges Merjane C, Jonas PM. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In: Intrinsic Activity. Vol 7. Austrian Pharmacological Society; 2019. doi:10.25006/ia.7.s1-a3.27' apa: 'Kim, O., Borges Merjane, C., & Jonas, P. M. (2019). Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In Intrinsic Activity (Vol. 7). Innsbruck, Austria: Austrian Pharmacological Society. https://doi.org/10.25006/ia.7.s1-a3.27' chicago: Kim, Olena, Carolina Borges Merjane, and Peter M Jonas. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” In Intrinsic Activity, Vol. 7. Austrian Pharmacological Society, 2019. https://doi.org/10.25006/ia.7.s1-a3.27. ieee: O. Kim, C. Borges Merjane, and P. M. Jonas, “Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy,” in Intrinsic Activity, Innsbruck, Austria, 2019, vol. 7, no. Suppl. 1. ista: 'Kim O, Borges Merjane C, Jonas PM. 2019. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. Intrinsic Activity. ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society vol. 7, A3.27.' mla: Kim, Olena, et al. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” Intrinsic Activity, vol. 7, no. Suppl. 1, A3.27, Austrian Pharmacological Society, 2019, doi:10.25006/ia.7.s1-a3.27. short: O. Kim, C. Borges Merjane, P.M. Jonas, in:, Intrinsic Activity, Austrian Pharmacological Society, 2019. conference: end_date: 2019-09-27 location: Innsbruck, Austria name: 'ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society' start_date: 2019-09-25 date_created: 2022-04-20T15:06:05Z date_published: 2019-09-11T00:00:00Z date_updated: 2024-03-27T23:30:07Z day: '11' department: - _id: PeJo doi: 10.25006/ia.7.s1-a3.27 ec_funded: 1 intvolume: ' 7' issue: Suppl. 1 keyword: - hippocampus - mossy fibers - readily releasable pool - electron microscopy language: - iso: eng main_file_link: - open_access: '1' url: https://www.intrinsicactivity.org/2019/7/S1/A3.27/ month: '09' oa: 1 oa_version: Published Version 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: 25BAF7B2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '708497' name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse - _id: 25C3DBB6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01205 name: Zellkommunikation in Gesundheit und Krankheit - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Intrinsic Activity publication_identifier: issn: - 2309-8503 publication_status: published publisher: Austrian Pharmacological Society quality_controlled: '1' related_material: record: - id: '11196' relation: dissertation_contains status: public status: public title: Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy type: conference_abstract user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 7 year: '2019' ... --- _id: '6363' abstract: - lang: eng text: "Distinguishing between similar experiences is achieved by the brain \ in a process called pattern separation. In the hippocampus, pattern \ separation reduces the interference of memories and increases the storage capacity by decorrelating similar inputs patterns of neuronal activity into \ non-overlapping output firing patterns. Winners-take-all (WTA) mechanism \ is a theoretical model for pattern separation in which a \"winner\" \ cell suppresses the activity of the neighboring neurons through feedback inhibition. However, if the network properties of the dentate gyrus support WTA as a biologically conceivable model remains unknown. Here, we showed that the connectivity rules of PV+interneurons and their synaptic properties are optimizedfor efficient pattern separation. We found using multiple whole-cell in vitrorecordings that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition, a form of feedback inhibition in which a GC inhibits other GCs but not \ itself through the activation of PV+interneurons. Thus, lateral inhibition between GC–PV+interneurons was ~10 times more abundant than recurrent connections. Furthermore, the GC–PV+interneuron connectivity was more spatially confined \ but less abundant than PV+interneurons–GC connectivity, leading to an \ asymmetrical distribution of excitatory and inhibitory connectivity. Our network model of the dentate gyrus with incorporated real connectivity rules efficiently decorrelates neuronal activity patterns using WTA as the primary mechanism. \ This process relied on lateral inhibition, fast-signaling properties of \ PV+interneurons and the asymmetrical distribution of excitatory and inhibitory connectivity. Finally, we found that silencing the activity of PV+interneurons in vivoleads to acute deficits in discrimination between similar environments, suggesting that PV+interneuron networks are necessary for behavioral relevant computations. Our results demonstrate that PV+interneurons possess unique connectivity and fast signaling properties that confer to the dentate \ gyrus network properties that allow the emergence of pattern separation. Thus, our results contribute to the knowledge of how specific forms of network organization underlie sophisticated types of information processing. \r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 citation: ama: Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363 apa: Espinoza Martinez, C. (2019). Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6363 chicago: Espinoza Martinez, Claudia . “Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6363. ieee: C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits,” Institute of Science and Technology Austria, 2019. ista: Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. mla: Espinoza Martinez, Claudia. Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6363. short: C. Espinoza Martinez, Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits, Institute of Science and Technology Austria, 2019. date_created: 2019-04-30T11:56:10Z date_published: 2019-04-30T00:00:00Z date_updated: 2023-09-15T12:03:48Z day: '30' ddc: - '570' degree_awarded: PhD department: - _id: PeJo doi: 10.15479/AT:ISTA:6363 file: - access_level: open_access checksum: 77c6c05cfe8b58c8abcf1b854375d084 content_type: application/pdf creator: cespinoza date_created: 2019-05-07T16:00:39Z date_updated: 2021-02-11T11:17:15Z embargo: 2020-05-09 file_id: '6389' file_name: Espinozathesis_all2.pdf file_size: 13966891 relation: main_file - access_level: closed checksum: f6aa819f127691a2b0fc21c76eb09746 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cespinoza date_created: 2019-05-07T16:00:48Z date_updated: 2020-07-14T12:47:28Z embargo_to: open_access file_id: '6390' file_name: Espinoza_Thesis.docx file_size: 11159900 relation: source_file file_date_updated: 2021-02-11T11:17:15Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '140' publication_identifier: isbn: - 978-3-99078-000-8 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '21' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '320' abstract: - lang: eng text: 'Fast-spiking, parvalbumin-expressing GABAergic interneurons (PV+-BCs) express a complex machinery of rapid signaling mechanisms, including specialized voltage-gated ion channels to generate brief action potentials (APs). However, short APs are associated with overlapping Na+ and K+ fluxes and are therefore energetically expensive. How the potentially vicious combination of high AP frequency and inefficient spike generation can be reconciled with limited energy supply is presently unclear. To address this question, we performed direct recordings from the PV+-BC axon, the subcellular structure where active conductances for AP initiation and propagation are located. Surprisingly, the energy required for the AP was, on average, only ∼1.6 times the theoretical minimum. High energy efficiency emerged from the combination of fast inactivation of Na+ channels and delayed activation of Kv3-type K+ channels, which minimized ion flux overlap during APs. Thus, the complementary tuning of axonal Na+ and K+ channel gating optimizes both fast signaling properties and metabolic efficiency. Hu et al. demonstrate that action potentials in parvalbumin-expressing GABAergic interneuron axons are energetically efficient, which is highly unexpected given their brief duration. High energy efficiency emerges from the combination of fast inactivation of voltage-gated Na+ channels and delayed activation of Kv3 channels in the axon. ' article_processing_charge: Yes (in subscription journal) author: - first_name: Hua full_name: Hu, Hua id: 4AC0145C-F248-11E8-B48F-1D18A9856A87 last_name: Hu - first_name: Fabian full_name: Roth, Fabian last_name: Roth - 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: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Hu H, Roth F, Vandael DH, Jonas PM. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. 2018;98(1):156-165. doi:10.1016/j.neuron.2018.02.024 apa: Hu, H., Roth, F., Vandael, D. H., & Jonas, P. M. (2018). Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2018.02.024 chicago: Hu, Hua, Fabian Roth, David H Vandael, and Peter M Jonas. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” Neuron. Elsevier, 2018. https://doi.org/10.1016/j.neuron.2018.02.024. ieee: H. Hu, F. Roth, D. H. Vandael, and P. M. Jonas, “Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons,” Neuron, vol. 98, no. 1. Elsevier, pp. 156–165, 2018. ista: Hu H, Roth F, Vandael DH, Jonas PM. 2018. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. 98(1), 156–165. mla: Hu, Hua, et al. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” Neuron, vol. 98, no. 1, Elsevier, 2018, pp. 156–65, doi:10.1016/j.neuron.2018.02.024. short: H. Hu, F. Roth, D.H. Vandael, P.M. Jonas, Neuron 98 (2018) 156–165. date_created: 2018-12-11T11:45:48Z date_published: 2018-04-04T00:00:00Z date_updated: 2023-09-11T12:45:10Z day: '04' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.neuron.2018.02.024 ec_funded: 1 external_id: isi: - '000429192100016' file: - access_level: open_access checksum: 76070f3729f9c603e1080d0151aa2b11 content_type: application/pdf creator: dernst date_created: 2018-12-17T10:37:50Z date_updated: 2020-07-14T12:46:03Z file_id: '5690' file_name: 2018_Neuron_Hu.pdf file_size: 3180444 relation: main_file file_date_updated: 2020-07-14T12:46:03Z has_accepted_license: '1' intvolume: ' 98' isi: 1 issue: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: 156 - 165 project: - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize publication: Neuron publication_status: published publisher: Elsevier publist_id: '7545' quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/a-certain-type-of-neurons-is-more-energy-efficient-than-previously-assumed/ scopus_import: '1' status: public title: Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 98 year: '2018' ... --- _id: '324' abstract: - lang: eng text: Neuronal networks in the brain consist of two main types of neuron, glutamatergic principal neurons and GABAergic interneurons. Although these interneurons only represent 10–20% of the whole population, they mediate feedback and feedforward inhibition and are involved in the generation of high-frequency network oscillations. A hallmark functional property of GABAergic interneurons, especially of the parvalbumin‑expressing (PV+) subtypes, is the speed of signaling at their output synapse across species and brain regions. Several molecular and subcellular factors may underlie the submillisecond signaling at GABAergic synapses. Such as the selective use of P/Q type Ca2+ channels and the tight coupling between Ca2+ channels and Ca2+ sensors of exocytosis. However, whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Besides, these interneurons are mainly show depression in response to train of stimuli. How could they keep sufficient release to control the activity of postsynaptic principal neurons during high network activity, is largely elusive. For my Ph.D. work, we firstly examined the Ca2+ sensor of exocytosis at the GABAergic basket cell (BC) to Purkinje cell (PC) synapse in the cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ~10% compared to the wild-type control, identifying Syt2 as the major Ca2+ sensor at BC‑PC synapses. Differential adenovirus-mediated rescue revealed Syt2 triggered release with shorter latency and higher temporal precision, and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as the release sensor at BC–PC synapse ensures fast feedforward inhibition in cerebellar microcircuits. Additionally, we tested the function of another synaptotagmin member, Syt7, for inhibitory synaptic transmission at the BC–PC synapse. Syt7 is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, it is strongly expressed in fast-spiking, PV+ GABAergic interneurons and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. How could Syt7, a facilitation sensor, contribute to the depressed inhibitory synaptic transmission needs to be further investigated and understood. Our results indicated that at the BC–PC synapse, Syt7 contributes to asynchronous release, pool replenishment and facilitation. In combination, these three effects ensure efficient transmitter release during high‑frequency activity and guarantee frequency independence of inhibition. Taken together, our results confirmed that Syt2, which has the fastest kinetic properties among all synaptotagmin members, is mainly used by the inhibitory BC‑PC synapse for synaptic transmission, contributing to the speed and temporal precision of transmitter release. Furthermore, we showed that Syt7, another highly expressed synaptotagmin member in the output synapses of cerebellar BCs, is used for ensuring efficient inhibitor synaptic transmission during high activity. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen citation: ama: Chen C. Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. 2018. doi:10.15479/AT:ISTA:th_997 apa: Chen, C. (2018). Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_997 chicago: Chen, Chong. “Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_997. ieee: C. Chen, “Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release,” Institute of Science and Technology Austria, 2018. ista: Chen C. 2018. Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. Institute of Science and Technology Austria. mla: Chen, Chong. Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_997. short: C. Chen, Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release, Institute of Science and Technology Austria, 2018. date_created: 2018-12-11T11:45:49Z date_published: 2018-03-01T00:00:00Z date_updated: 2023-09-27T12:26:03Z day: '01' ddc: - '571' degree_awarded: PhD department: - _id: PeJo doi: 10.15479/AT:ISTA:th_997 file: - access_level: open_access checksum: 8e163ae9e927401b9fa7c1b3e6a3631a content_type: application/pdf creator: system date_created: 2018-12-12T10:13:58Z date_updated: 2020-07-14T12:46:04Z file_id: '5046' file_name: IST-2018-997-v1+1_Thesis_chong_a.pdf file_size: 8719458 relation: main_file - access_level: closed checksum: f7d7260029a5fbb5c982db61328ade52 content_type: application/octet-stream creator: dernst date_created: 2019-04-05T09:25:26Z date_updated: 2020-07-14T12:46:04Z file_id: '6221' file_name: 2018_Thesis_chong_source.pages file_size: 47841940 relation: source_file file_date_updated: 2020-07-14T12:46:04Z has_accepted_license: '1' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: '110' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '7541' pubrep_id: '997' related_material: record: - id: '1117' relation: part_of_dissertation status: public - id: '749' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release 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: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2018' ... --- _id: '21' abstract: - lang: eng text: Parvalbumin-positive (PV+) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV+ interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV+ interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations acknowledgement: This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award), both to P.J.. article_number: '4605' article_processing_charge: No article_type: original author: - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán orcid: 0000-0003-2209-5242 - first_name: Xiaomin full_name: Zhang, Xiaomin id: 423EC9C2-F248-11E8-B48F-1D18A9856A87 last_name: Zhang - 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: Espinoza Martinez C, Guzmán J, Zhang X, Jonas PM. Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-06899-3 apa: Espinoza Martinez, C., Guzmán, J., Zhang, X., & Jonas, P. M. (2018). Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-018-06899-3 chicago: Espinoza Martinez, Claudia , José Guzmán, Xiaomin Zhang, and Peter M Jonas. “Parvalbumin+ Interneurons Obey Unique Connectivity Rules and Establish a Powerful Lateral-Inhibition Microcircuit in Dentate Gyrus.” Nature Communications. Nature Publishing Group, 2018. https://doi.org/10.1038/s41467-018-06899-3. ieee: C. Espinoza Martinez, J. Guzmán, X. Zhang, and P. M. Jonas, “Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus,” Nature Communications, vol. 9, no. 1. Nature Publishing Group, 2018. ista: Espinoza Martinez C, Guzmán J, Zhang X, Jonas PM. 2018. Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. 9(1), 4605. mla: Espinoza Martinez, Claudia, et al. “Parvalbumin+ Interneurons Obey Unique Connectivity Rules and Establish a Powerful Lateral-Inhibition Microcircuit in Dentate Gyrus.” Nature Communications, vol. 9, no. 1, 4605, Nature Publishing Group, 2018, doi:10.1038/s41467-018-06899-3. short: C. Espinoza Martinez, J. Guzmán, X. Zhang, P.M. Jonas, Nature Communications 9 (2018). date_created: 2018-12-11T11:44:12Z date_published: 2018-11-02T00:00:00Z date_updated: 2024-03-27T23:30:31Z day: '02' ddc: - '570' department: - _id: PeJo doi: 10.1038/s41467-018-06899-3 ec_funded: 1 external_id: isi: - '000449069700009' file: - access_level: open_access checksum: 9fe2a63bd95a5067d896c087d07998f3 content_type: application/pdf creator: dernst date_created: 2018-12-17T15:41:57Z date_updated: 2020-07-14T12:45:28Z file_id: '5715' file_name: 2018_NatureComm_Espinoza.pdf file_size: 4651930 relation: main_file file_date_updated: 2020-07-14T12:45:28Z has_accepted_license: '1' intvolume: ' 9' isi: 1 issue: '1' language: - iso: eng month: '11' oa: 1 oa_version: Published Version 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 publication: Nature Communications publication_status: published publisher: Nature Publishing Group publist_id: '8034' quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/lateral-inhibition-keeps-similar-memories-apart/ record: - id: '6363' relation: dissertation_contains status: public scopus_import: '1' status: public title: Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus 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: 9 year: '2018' ... --- _id: '630' abstract: - lang: eng text: 'Background: Standards have become available to share semantically encoded vital parameters from medical devices, as required for example by personal healthcare records. Standardised sharing of biosignal data largely remains open. Objectives: The goal of this work is to explore available biosignal file format and data exchange standards and profiles, and to conceptualise end-To-end solutions. Methods: The authors reviewed and discussed available biosignal file format standards with other members of international standards development organisations (SDOs). Results: A raw concept for standards based acquisition, storage, archiving and sharing of biosignals was developed. The GDF format may serve for storing biosignals. Signals can then be shared using FHIR resources and may be stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible format. Conclusion: Currently a group of international SDOs (e.g. HL7, IHE, DICOM, IEEE) is engaged in intensive discussions. This discussion extends existing work that already was adopted by large implementer communities. The concept presented here only reports the current status of the discussion in Austria. The discussion will continue internationally, with results to be expected over the coming years.' alternative_title: - Studies in Health Technology and Informatics author: - first_name: Stefan full_name: Sauermann, Stefan last_name: Sauermann - first_name: Veronika full_name: David, Veronika last_name: David - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: Reinhard full_name: Egelkraut, Reinhard last_name: Egelkraut - first_name: Matthias full_name: Frohner, Matthias last_name: Frohner - first_name: Birgit full_name: Pohn, Birgit last_name: Pohn - first_name: Philipp full_name: Urbauer, Philipp last_name: Urbauer - first_name: Alexander full_name: Mense, Alexander last_name: Mense citation: ama: 'Sauermann S, David V, Schlögl A, et al. Biosignals standards and FHIR: The way to go. In: Vol 236. IOS Press; 2017:356-362. doi:10.3233/978-1-61499-759-7-356' apa: 'Sauermann, S., David, V., Schlögl, A., Egelkraut, R., Frohner, M., Pohn, B., … Mense, A. (2017). Biosignals standards and FHIR: The way to go (Vol. 236, pp. 356–362). Presented at the eHealth: Health Informatics Meets eHealth, Vienna, Austria: IOS Press. https://doi.org/10.3233/978-1-61499-759-7-356' chicago: 'Sauermann, Stefan, Veronika David, Alois Schlögl, Reinhard Egelkraut, Matthias Frohner, Birgit Pohn, Philipp Urbauer, and Alexander Mense. “Biosignals Standards and FHIR: The Way to Go,” 236:356–62. IOS Press, 2017. https://doi.org/10.3233/978-1-61499-759-7-356.' ieee: 'S. Sauermann et al., “Biosignals standards and FHIR: The way to go,” presented at the eHealth: Health Informatics Meets eHealth, Vienna, Austria, 2017, vol. 236, pp. 356–362.' ista: 'Sauermann S, David V, Schlögl A, Egelkraut R, Frohner M, Pohn B, Urbauer P, Mense A. 2017. Biosignals standards and FHIR: The way to go. eHealth: Health Informatics Meets eHealth, Studies in Health Technology and Informatics, vol. 236, 356–362.' mla: 'Sauermann, Stefan, et al. Biosignals Standards and FHIR: The Way to Go. Vol. 236, IOS Press, 2017, pp. 356–62, doi:10.3233/978-1-61499-759-7-356.' short: S. Sauermann, V. David, A. Schlögl, R. Egelkraut, M. Frohner, B. Pohn, P. Urbauer, A. Mense, in:, IOS Press, 2017, pp. 356–362. conference: end_date: 2017-05-24 location: Vienna, Austria name: 'eHealth: Health Informatics Meets eHealth' start_date: 2017-05-23 date_created: 2018-12-11T11:47:36Z date_published: 2017-01-01T00:00:00Z date_updated: 2021-01-12T08:06:59Z day: '01' ddc: - '005' department: - _id: ScienComp - _id: PeJo doi: 10.3233/978-1-61499-759-7-356 file: - access_level: open_access checksum: 1254dcc5b04a996d97fad9a726b42727 content_type: application/pdf creator: system date_created: 2018-12-12T10:11:56Z date_updated: 2020-07-14T12:47:27Z file_id: '4913' file_name: IST-2017-906-v1+1_SHTI236-0356.pdf file_size: 443635 relation: main_file file_date_updated: 2020-07-14T12:47:27Z has_accepted_license: '1' intvolume: ' 236' language: - iso: eng license: https://creativecommons.org/licenses/by-nc/4.0/ month: '01' oa: 1 oa_version: Published Version page: 356 - 362 publication_identifier: isbn: - 978-161499758-0 publication_status: published publisher: IOS Press publist_id: '7164' pubrep_id: '906' quality_controlled: '1' scopus_import: 1 status: public title: 'Biosignals standards and FHIR: The way to go' 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: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 236 year: '2017' ... --- _id: '706' abstract: - lang: eng text: A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse. We investigated here the roles of afadin in the functional differentiations of the mossy fiber synapse using the afadin-deficient mice. The electrophysiological studies showed that both the release probability of glutamate and the postsynaptic responsiveness to glutamate were markedly reduced, but not completely lost, in the afadin-deficient mossy fiber synapse, whereas neither long-term potentiation nor long-term depression was affected. These results indicate that afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse. author: - first_name: Xiaoqi full_name: Geng, Xiaoqi id: 3395256A-F248-11E8-B48F-1D18A9856A87 last_name: Geng - first_name: Tomohiko full_name: Maruo, Tomohiko last_name: Maruo - first_name: Kenji full_name: Mandai, Kenji last_name: Mandai - first_name: Irwan full_name: Supriyanto, Irwan last_name: Supriyanto - first_name: Muneaki full_name: Miyata, Muneaki last_name: Miyata - first_name: Shotaro full_name: Sakakibara, Shotaro last_name: Sakakibara - first_name: Akira full_name: Mizoguchi, Akira last_name: Mizoguchi - first_name: Yoshimi full_name: Takai, Yoshimi last_name: Takai - first_name: Masahiro full_name: Mori, Masahiro last_name: Mori citation: ama: Geng X, Maruo T, Mandai K, et al. Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. Genes to Cells. 2017;22(8):715-722. doi:10.1111/gtc.12508 apa: Geng, X., Maruo, T., Mandai, K., Supriyanto, I., Miyata, M., Sakakibara, S., … Mori, M. (2017). Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. Genes to Cells. Wiley-Blackwell. https://doi.org/10.1111/gtc.12508 chicago: Geng, Xiaoqi, Tomohiko Maruo, Kenji Mandai, Irwan Supriyanto, Muneaki Miyata, Shotaro Sakakibara, Akira Mizoguchi, Yoshimi Takai, and Masahiro Mori. “Roles of Afadin in Functional Differentiations of Hippocampal Mossy Fiber Synapse.” Genes to Cells. Wiley-Blackwell, 2017. https://doi.org/10.1111/gtc.12508. ieee: X. Geng et al., “Roles of afadin in functional differentiations of hippocampal mossy fiber synapse,” Genes to Cells, vol. 22, no. 8. Wiley-Blackwell, pp. 715–722, 2017. ista: Geng X, Maruo T, Mandai K, Supriyanto I, Miyata M, Sakakibara S, Mizoguchi A, Takai Y, Mori M. 2017. Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. Genes to Cells. 22(8), 715–722. mla: Geng, Xiaoqi, et al. “Roles of Afadin in Functional Differentiations of Hippocampal Mossy Fiber Synapse.” Genes to Cells, vol. 22, no. 8, Wiley-Blackwell, 2017, pp. 715–22, doi:10.1111/gtc.12508. short: X. Geng, T. Maruo, K. Mandai, I. Supriyanto, M. Miyata, S. Sakakibara, A. Mizoguchi, Y. Takai, M. Mori, Genes to Cells 22 (2017) 715–722. date_created: 2018-12-11T11:48:02Z date_published: 2017-08-01T00:00:00Z date_updated: 2021-01-12T08:11:37Z day: '01' department: - _id: PeJo doi: 10.1111/gtc.12508 intvolume: ' 22' issue: '8' language: - iso: eng month: '08' oa_version: None page: 715 - 722 publication: Genes to Cells publication_identifier: issn: - '13569597' publication_status: published publisher: Wiley-Blackwell publist_id: '6987' quality_controlled: '1' scopus_import: 1 status: public title: Roles of afadin in functional differentiations of hippocampal mossy fiber synapse type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 22 year: '2017' ... --- _id: '1118' abstract: - lang: eng text: Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo. acknowledged_ssus: - _id: M-Shop - _id: ScienComp - _id: PreCl article_processing_charge: No author: - first_name: Jian full_name: Gan, Jian id: 3614E438-F248-11E8-B48F-1D18A9856A87 last_name: Gan - first_name: Shih-Ming full_name: Weng, Shih-Ming id: 2F9C5AC8-F248-11E8-B48F-1D18A9856A87 last_name: Weng - first_name: Alejandro full_name: Pernia-Andrade, Alejandro id: 36963E98-F248-11E8-B48F-1D18A9856A87 last_name: Pernia-Andrade - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 - 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: Gan J, Weng S-M, Pernia-Andrade A, Csicsvari JL, Jonas PM. Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. Neuron. 2017;93(2):308-314. doi:10.1016/j.neuron.2016.12.018 apa: Gan, J., Weng, S.-M., Pernia-Andrade, A., Csicsvari, J. L., & Jonas, P. M. (2017). Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2016.12.018 chicago: Gan, Jian, Shih-Ming Weng, Alejandro Pernia-Andrade, Jozsef L Csicsvari, and Peter M Jonas. “Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice in Vivo.” Neuron. Elsevier, 2017. https://doi.org/10.1016/j.neuron.2016.12.018. ieee: J. Gan, S.-M. Weng, A. Pernia-Andrade, J. L. Csicsvari, and P. M. Jonas, “Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo,” Neuron, vol. 93, no. 2. Elsevier, pp. 308–314, 2017. ista: Gan J, Weng S-M, Pernia-Andrade A, Csicsvari JL, Jonas PM. 2017. Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. Neuron. 93(2), 308–314. mla: Gan, Jian, et al. “Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice in Vivo.” Neuron, vol. 93, no. 2, Elsevier, 2017, pp. 308–14, doi:10.1016/j.neuron.2016.12.018. short: J. Gan, S.-M. Weng, A. Pernia-Andrade, J.L. Csicsvari, P.M. Jonas, Neuron 93 (2017) 308–314. date_created: 2018-12-11T11:50:15Z date_published: 2017-01-18T00:00:00Z date_updated: 2023-09-20T11:31:48Z day: '18' ddc: - '571' department: - _id: PeJo - _id: JoCs doi: 10.1016/j.neuron.2016.12.018 ec_funded: 1 external_id: isi: - '000396428200010' file: - access_level: open_access content_type: application/pdf creator: system date_created: 2018-12-12T10:08:56Z date_updated: 2018-12-12T10:08:56Z file_id: '4719' file_name: IST-2017-752-v1+1_1-s2.0-S0896627316309606-main.pdf file_size: 2738950 relation: main_file file_date_updated: 2018-12-12T10:08:56Z has_accepted_license: '1' intvolume: ' 93' isi: 1 issue: '2' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 308 - 314 project: - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons publication: Neuron publication_status: published publisher: Elsevier publist_id: '6244' pubrep_id: '752' quality_controlled: '1' scopus_import: '1' status: public title: Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 93 year: '2017' ... --- _id: '1117' abstract: - lang: eng text: 'GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author' acknowledged_ssus: - _id: Bio - _id: PreCl article_processing_charge: No author: - 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: Rachel full_name: Satterield, Rachel last_name: Satterield - first_name: Samuel full_name: Young, Samuel last_name: Young - 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 C, Arai itaru, Satterield R, Young S, Jonas PM. Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 2017;18(3):723-736. doi:10.1016/j.celrep.2016.12.067 apa: Chen, C., Arai, itaru, Satterield, R., Young, S., & Jonas, P. M. (2017). Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2016.12.067 chicago: Chen, Chong, itaru Arai, Rachel Satterield, Samuel Young, and Peter M Jonas. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2016.12.067. ieee: C. Chen, itaru Arai, R. Satterield, S. Young, and P. M. Jonas, “Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse,” Cell Reports, vol. 18, no. 3. Cell Press, pp. 723–736, 2017. ista: Chen C, Arai itaru, Satterield R, Young S, Jonas PM. 2017. Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 18(3), 723–736. mla: Chen, Chong, et al. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” Cell Reports, vol. 18, no. 3, Cell Press, 2017, pp. 723–36, doi:10.1016/j.celrep.2016.12.067. short: C. Chen, itaru Arai, R. Satterield, S. Young, P.M. Jonas, Cell Reports 18 (2017) 723–736. date_created: 2018-12-11T11:50:14Z date_published: 2017-01-17T00:00:00Z date_updated: 2023-09-20T11:32:15Z day: '17' ddc: - '571' department: - _id: PeJo doi: 10.1016/j.celrep.2016.12.067 ec_funded: 1 external_id: isi: - '000396470600013' file: - access_level: open_access content_type: application/pdf creator: system date_created: 2018-12-12T10:16:09Z date_updated: 2018-12-12T10:16:09Z file_id: '5195' file_name: IST-2017-751-v1+1_1-s2.0-S2211124716317740-main.pdf file_size: 4427591 relation: main_file file_date_updated: 2018-12-12T10:16:09Z has_accepted_license: '1' intvolume: ' 18' isi: 1 issue: '3' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 723 - 736 project: - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons publication: Cell Reports publication_identifier: issn: - '22111247' publication_status: published publisher: Cell Press publist_id: '6245' pubrep_id: '751' quality_controlled: '1' related_material: record: - id: '324' relation: dissertation_contains status: public scopus_import: '1' status: public title: Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 18 year: '2017' ... --- _id: '991' abstract: - lang: eng text: Synaptotagmin 7 (Syt7) was originally identified as a slow Ca2+ sensor for lysosome fusion, but its function at fast synapses is controversial. The paper by Luo and Südhof (2017) in this issue of Neuron shows that at the calyx of Held in the auditory brainstem Syt7 triggers asynchronous release during stimulus trains, resulting in reliable and temporally precise high-frequency transmission. Thus, a slow Ca2+ sensor contributes to the fast signaling properties of the calyx synapse. article_processing_charge: No author: - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen - 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 C, Jonas PM. Synaptotagmins: That’s why so many. Neuron. 2017;94(4):694-696. doi:10.1016/j.neuron.2017.05.011' apa: 'Chen, C., & Jonas, P. M. (2017). Synaptotagmins: That’s why so many. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2017.05.011' chicago: 'Chen, Chong, and Peter M Jonas. “Synaptotagmins: That’s Why so Many.” Neuron. Elsevier, 2017. https://doi.org/10.1016/j.neuron.2017.05.011.' ieee: 'C. Chen and P. M. Jonas, “Synaptotagmins: That’s why so many,” Neuron, vol. 94, no. 4. Elsevier, pp. 694–696, 2017.' ista: 'Chen C, Jonas PM. 2017. Synaptotagmins: That’s why so many. Neuron. 94(4), 694–696.' mla: 'Chen, Chong, and Peter M. Jonas. “Synaptotagmins: That’s Why so Many.” Neuron, vol. 94, no. 4, Elsevier, 2017, pp. 694–96, doi:10.1016/j.neuron.2017.05.011.' short: C. Chen, P.M. Jonas, Neuron 94 (2017) 694–696. date_created: 2018-12-11T11:49:34Z date_published: 2017-05-17T00:00:00Z date_updated: 2023-09-22T09:54:37Z day: '17' department: - _id: PeJo doi: 10.1016/j.neuron.2017.05.011 external_id: isi: - '000401415100002' intvolume: ' 94' isi: 1 issue: '4' language: - iso: eng month: '05' oa_version: None page: 694 - 696 publication: Neuron publication_identifier: issn: - '08966273' publication_status: published publisher: Elsevier publist_id: '6408' quality_controlled: '1' scopus_import: '1' status: public title: 'Synaptotagmins: That’s why so many' type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 94 year: '2017' ... --- _id: '800' abstract: - lang: eng text: Gamma oscillations (30–150 Hz) in neuronal networks are associated with the processing and recall of information. We measured local field potentials in the dentate gyrus of freely moving mice and found that gamma activity occurs in bursts, which are highly heterogeneous in their spatial extensions, ranging from focal to global coherent events. Synaptic communication among perisomatic-inhibitory interneurons (PIIs) is thought to play an important role in the generation of hippocampal gamma patterns. However, how neuronal circuits can generate synchronous oscillations at different spatial scales is unknown. We analyzed paired recordings in dentate gyrus slices and show that synaptic signaling at interneuron-interneuron synapses is distance dependent. Synaptic strength declines whereas the duration of inhibitory signals increases with axonal distance among interconnected PIIs. Using neuronal network modeling, we show that distance-dependent inhibition generates multiple highly synchronous focal gamma bursts allowing the network to process complex inputs in parallel in flexibly organized neuronal centers. article_number: '758' article_processing_charge: No author: - first_name: Michael full_name: Strüber, Michael last_name: Strüber - first_name: Jonas full_name: Sauer, Jonas last_name: Sauer - 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: Marlene full_name: Bartos, Marlene last_name: Bartos citation: ama: Strüber M, Sauer J, Jonas PM, Bartos M. Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus. Nature Communications. 2017;8(1). doi:10.1038/s41467-017-00936-3 apa: Strüber, M., Sauer, J., Jonas, P. M., & Bartos, M. (2017). Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-017-00936-3 chicago: Strüber, Michael, Jonas Sauer, Peter M Jonas, and Marlene Bartos. “Distance-Dependent Inhibition Facilitates Focality of Gamma Oscillations in the Dentate Gyrus.” Nature Communications. Nature Publishing Group, 2017. https://doi.org/10.1038/s41467-017-00936-3. ieee: M. Strüber, J. Sauer, P. M. Jonas, and M. Bartos, “Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus,” Nature Communications, vol. 8, no. 1. Nature Publishing Group, 2017. ista: Strüber M, Sauer J, Jonas PM, Bartos M. 2017. Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus. Nature Communications. 8(1), 758. mla: Strüber, Michael, et al. “Distance-Dependent Inhibition Facilitates Focality of Gamma Oscillations in the Dentate Gyrus.” Nature Communications, vol. 8, no. 1, 758, Nature Publishing Group, 2017, doi:10.1038/s41467-017-00936-3. short: M. Strüber, J. Sauer, P.M. Jonas, M. Bartos, Nature Communications 8 (2017). date_created: 2018-12-11T11:48:34Z date_published: 2017-10-02T00:00:00Z date_updated: 2023-09-27T10:59:41Z day: '02' ddc: - '571' department: - _id: PeJo doi: 10.1038/s41467-017-00936-3 ec_funded: 1 external_id: isi: - '000412053100004' file: - access_level: open_access checksum: 7e2c7621afd5f802338e92e8619f024d content_type: application/pdf creator: system date_created: 2018-12-12T10:15:17Z date_updated: 2020-07-14T12:48:07Z file_id: '5135' file_name: IST-2017-914-v1+1_s41467-017-00936-3.pdf file_size: 4261832 relation: main_file file_date_updated: 2020-07-14T12:48:07Z has_accepted_license: '1' intvolume: ' 8' isi: 1 issue: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version project: - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons publication: Nature Communications publication_identifier: issn: - '20411723' publication_status: published publisher: Nature Publishing Group publist_id: '6853' pubrep_id: '914' quality_controlled: '1' scopus_import: '1' status: public title: Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus 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: 8 year: '2017' ... --- _id: '749' abstract: - lang: eng text: 'Synaptotagmin 7 (Syt7) is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, Syt7 is strongly expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. To resolve this apparent contradiction, we examined the effects of genetic elimination of Syt7 on synaptic transmission at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum. Our results indicate that at the BC-PC synapse, Syt7 contributes to asynchronous release, pool replenishment, and facilitation. In combination, these three effects ensure efficient transmitter release during high-frequency activity and guarantee frequency independence of inhibition. Our results identify a distinct function of Syt7: ensuring the efficiency of high-frequency inhibitory synaptic transmission' acknowledged_ssus: - _id: PreCl article_processing_charge: No author: - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Rachel full_name: Satterfield, Rachel last_name: Satterfield - first_name: Samuel full_name: Young, Samuel last_name: Young - 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 C, Satterfield R, Young S, Jonas PM. Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses. Cell Reports. 2017;21(8):2082-2089. doi:10.1016/j.celrep.2017.10.122 apa: Chen, C., Satterfield, R., Young, S., & Jonas, P. M. (2017). Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2017.10.122 chicago: Chen, Chong, Rachel Satterfield, Samuel Young, and Peter M Jonas. “Triple Function of Synaptotagmin 7 Ensures Efficiency of High-Frequency Transmission at Central GABAergic Synapses.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2017.10.122. ieee: C. Chen, R. Satterfield, S. Young, and P. M. Jonas, “Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses,” Cell Reports, vol. 21, no. 8. Cell Press, pp. 2082–2089, 2017. ista: Chen C, Satterfield R, Young S, Jonas PM. 2017. Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses. Cell Reports. 21(8), 2082–2089. mla: Chen, Chong, et al. “Triple Function of Synaptotagmin 7 Ensures Efficiency of High-Frequency Transmission at Central GABAergic Synapses.” Cell Reports, vol. 21, no. 8, Cell Press, 2017, pp. 2082–89, doi:10.1016/j.celrep.2017.10.122. short: C. Chen, R. Satterfield, S. Young, P.M. Jonas, Cell Reports 21 (2017) 2082–2089. date_created: 2018-12-11T11:48:18Z date_published: 2017-11-21T00:00:00Z date_updated: 2023-09-27T12:26:04Z day: '21' ddc: - '570' - '571' department: - _id: PeJo doi: 10.1016/j.celrep.2017.10.122 ec_funded: 1 external_id: isi: - '000416216700007' file: - access_level: open_access checksum: a6afa3764909bf6edafa07982d8e1cee content_type: application/pdf creator: system date_created: 2018-12-12T10:09:14Z date_updated: 2020-07-14T12:47:59Z file_id: '4737' file_name: IST-2017-874-v1+1_PIIS2211124717316029.pdf file_size: 2759195 relation: main_file file_date_updated: 2020-07-14T12:47:59Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '8' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: 2082 - 2089 project: - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse publication: Cell Reports publication_identifier: issn: - '22111247' publication_status: published publisher: Cell Press publist_id: '6907' pubrep_id: '874' quality_controlled: '1' related_material: record: - id: '324' relation: dissertation_contains status: public scopus_import: '1' status: public title: Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 21 year: '2017' ... --- _id: '1142' abstract: - lang: eng text: Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders. acknowledgement: 'Y. Fukui (Medical Institute of Bioregulation, Kyushu University) and J. Stein (Theodor Kocher Institute, University of Bern) are acknowledged for providing the DOCK8 deficient bone marrow. and H. Häcker (St. Judes Children''s Research Hospital) for providing the ERHBD-HoxB8-encoding retroviral construct. pSpCas9(BB)-2a-Puro (PX459) was a gift from F. Zhang (Massachusetts Institute of Technology) (Addgene plasmid # 48139) and pGRG36 was a gift from N. Craig (Johns Hopkins University School of Medicine) (Addgene plasmid # 16666). LifeAct-GFP-encoding retrovirus was kindly provided by A. Leithner (Institute of Science and Technology Austria). pSIM8 and TKC E. coli were gifts from D.L. Court (Center for Cancer Research, National Cancer Institute). We acknowledge M. Gröger and S. Rauscher for excellent technical support (Core imaging facility, Medical University of Vienna). We thank D.P. Barlow and L.R. Cheever for critical reading of the manuscript. This work was supported by the Austrian Academy of Sciences, the Science Fund of the Austrian National Bank (14107) and the Austrian Science Fund FWF (I1620-B22) in the Infect-ERA framework (to S.Knapp).' author: - first_name: Rui full_name: Martins, Rui last_name: Martins - first_name: Julia full_name: Maier, Julia last_name: Maier - first_name: Anna full_name: Gorki, Anna last_name: Gorki - first_name: Kilian full_name: Huber, Kilian last_name: Huber - first_name: Omar full_name: Sharif, Omar last_name: Sharif - first_name: Philipp full_name: Starkl, Philipp last_name: Starkl - first_name: Simona full_name: Saluzzo, Simona last_name: Saluzzo - first_name: Federica full_name: Quattrone, Federica last_name: Quattrone - first_name: Riem full_name: Gawish, Riem last_name: Gawish - first_name: Karin full_name: Lakovits, Karin last_name: Lakovits - first_name: Michael full_name: Aichinger, Michael last_name: Aichinger - first_name: Branka full_name: Radic Sarikas, Branka last_name: Radic Sarikas - first_name: Charles full_name: Lardeau, Charles last_name: Lardeau - first_name: Anastasiya full_name: Hladik, Anastasiya last_name: Hladik - first_name: Ana full_name: Korosec, Ana last_name: Korosec - first_name: Markus full_name: Brown, Markus id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87 last_name: Brown - first_name: Kari full_name: Vaahtomeri, Kari id: 368EE576-F248-11E8-B48F-1D18A9856A87 last_name: Vaahtomeri orcid: 0000-0001-7829-3518 - first_name: Michelle full_name: Duggan, Michelle id: 2EDEA62C-F248-11E8-B48F-1D18A9856A87 last_name: Duggan - first_name: Dontscho full_name: Kerjaschki, Dontscho last_name: Kerjaschki - first_name: Harald full_name: Esterbauer, Harald last_name: Esterbauer - first_name: Jacques full_name: Colinge, Jacques last_name: Colinge - first_name: Stephanie full_name: Eisenbarth, Stephanie last_name: Eisenbarth - first_name: Thomas full_name: Decker, Thomas last_name: Decker - first_name: Keiryn full_name: Bennett, Keiryn last_name: Bennett - first_name: Stefan full_name: Kubicek, Stefan last_name: Kubicek - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 - first_name: Giulio full_name: Superti Furga, Giulio last_name: Superti Furga - first_name: Sylvia full_name: Knapp, Sylvia last_name: Knapp citation: ama: Martins R, Maier J, Gorki A, et al. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. 2016;17(12):1361-1372. doi:10.1038/ni.3590 apa: Martins, R., Maier, J., Gorki, A., Huber, K., Sharif, O., Starkl, P., … Knapp, S. (2016). Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3590 chicago: Martins, Rui, Julia Maier, Anna Gorki, Kilian Huber, Omar Sharif, Philipp Starkl, Simona Saluzzo, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” Nature Immunology. Nature Publishing Group, 2016. https://doi.org/10.1038/ni.3590. ieee: R. Martins et al., “Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions,” Nature Immunology, vol. 17, no. 12. Nature Publishing Group, pp. 1361–1372, 2016. ista: Martins R, Maier J, Gorki A, Huber K, Sharif O, Starkl P, Saluzzo S, Quattrone F, Gawish R, Lakovits K, Aichinger M, Radic Sarikas B, Lardeau C, Hladik A, Korosec A, Brown M, Vaahtomeri K, Duggan M, Kerjaschki D, Esterbauer H, Colinge J, Eisenbarth S, Decker T, Bennett K, Kubicek S, Sixt MK, Superti Furga G, Knapp S. 2016. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. 17(12), 1361–1372. mla: Martins, Rui, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” Nature Immunology, vol. 17, no. 12, Nature Publishing Group, 2016, pp. 1361–72, doi:10.1038/ni.3590. short: R. Martins, J. Maier, A. Gorki, K. Huber, O. Sharif, P. Starkl, S. Saluzzo, F. Quattrone, R. Gawish, K. Lakovits, M. Aichinger, B. Radic Sarikas, C. Lardeau, A. Hladik, A. Korosec, M. Brown, K. Vaahtomeri, M. Duggan, D. Kerjaschki, H. Esterbauer, J. Colinge, S. Eisenbarth, T. Decker, K. Bennett, S. Kubicek, M.K. Sixt, G. Superti Furga, S. Knapp, Nature Immunology 17 (2016) 1361–1372. date_created: 2018-12-11T11:50:22Z date_published: 2016-12-01T00:00:00Z date_updated: 2021-01-12T06:48:36Z day: '01' department: - _id: MiSi - _id: PeJo doi: 10.1038/ni.3590 intvolume: ' 17' issue: '12' language: - iso: eng main_file_link: - open_access: '1' url: https://ora.ox.ac.uk/objects/uuid:f53a464e-1e5b-4f08-a7d8-b6749b852b9d month: '12' oa: 1 oa_version: Submitted Version page: 1361 - 1372 publication: Nature Immunology publication_status: published publisher: Nature Publishing Group publist_id: '6216' quality_controlled: '1' scopus_import: 1 status: public title: Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 17 year: '2016' ... --- _id: '1323' abstract: - lang: eng text: Mossy fiber synapses on CA3 pyramidal cells are 'conditional detonators' that reliably discharge postsynaptic targets. The 'conditional' nature implies that burst activity in dentate gyrus granule cells is required for detonation. Whether single unitary excitatory postsynaptic potentials (EPSPs) trigger spikes in CA3 neurons remains unknown. Mossy fiber synapses exhibit both pronounced short-term facilitation and uniquely large post-tetanic potentiation (PTP). We tested whether PTP could convert mossy fiber synapses from subdetonator into detonator mode, using a recently developed method to selectively and noninvasively stimulate individual presynaptic terminals in rat brain slices. Unitary EPSPs failed to initiate a spike in CA3 neurons under control conditions, but reliably discharged them after induction of presynaptic short-term plasticity. Remarkably, PTP switched mossy fiber synapses into full detonators for tens of seconds. Plasticity-dependent detonation may be critical for efficient coding, storage, and recall of information in the granule cell–CA3 cell network. acknowledged_ssus: - _id: M-Shop - _id: PreCl article_number: e17977 author: - first_name: Nicholas full_name: Vyleta, Nicholas id: 36C4978E-F248-11E8-B48F-1D18A9856A87 last_name: Vyleta - 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: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Vyleta N, Borges Merjane C, Jonas PM. Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. eLife. 2016;5. doi:10.7554/eLife.17977 apa: Vyleta, N., Borges Merjane, C., & Jonas, P. M. (2016). Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.17977 chicago: Vyleta, Nicholas, Carolina Borges Merjane, and Peter M Jonas. “Plasticity-Dependent, Full Detonation at Hippocampal Mossy Fiber–CA3 Pyramidal Neuron Synapses.” ELife. eLife Sciences Publications, 2016. https://doi.org/10.7554/eLife.17977. ieee: N. Vyleta, C. Borges Merjane, and P. M. Jonas, “Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses,” eLife, vol. 5. eLife Sciences Publications, 2016. ista: Vyleta N, Borges Merjane C, Jonas PM. 2016. Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. eLife. 5, e17977. mla: Vyleta, Nicholas, et al. “Plasticity-Dependent, Full Detonation at Hippocampal Mossy Fiber–CA3 Pyramidal Neuron Synapses.” ELife, vol. 5, e17977, eLife Sciences Publications, 2016, doi:10.7554/eLife.17977. short: N. Vyleta, C. Borges Merjane, P.M. Jonas, ELife 5 (2016). date_created: 2018-12-11T11:51:22Z date_published: 2016-10-25T00:00:00Z date_updated: 2023-02-21T10:34:24Z day: '25' ddc: - '571' - '572' department: - _id: PeJo doi: 10.7554/eLife.17977 ec_funded: 1 file: - access_level: open_access checksum: a7201280c571bed88ebd459ce5ce6a47 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:05Z date_updated: 2020-07-14T12:44:44Z file_id: '5257' file_name: IST-2016-715-v1+1_e17977-download.pdf file_size: 1477891 relation: main_file file_date_updated: 2020-07-14T12:44:44Z has_accepted_license: '1' intvolume: ' 5' language: - iso: eng month: '10' oa: 1 oa_version: Published Version project: - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse publication: eLife publication_status: published publisher: eLife Sciences Publications publist_id: '5947' pubrep_id: '715' quality_controlled: '1' scopus_import: 1 status: public title: Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 5 year: '2016' ... --- _id: '1350' abstract: - lang: eng text: "The hippocampal CA3 region plays a key role in learning and memory. Recurrent CA3–CA3\r\nsynapses are thought to be the subcellular substrate of pattern completion. However, the\r\nsynaptic mechanisms of this network computation remain enigmatic. To investigate these mechanisms, we combined functional connectivity analysis with network modeling.\r\nSimultaneous recording fromup to eight CA3 pyramidal neurons revealed that connectivity was sparse, spatially uniform, and highly enriched in disynaptic motifs (reciprocal, convergence,divergence, and chain motifs). Unitary connections were composed of one or two synaptic contacts, suggesting efficient use of postsynaptic space. Real-size modeling indicated that CA3 networks with sparse connectivity, disynaptic motifs, and single-contact connections robustly generated pattern completion.Thus, macro- and microconnectivity contribute to efficient\r\nmemory storage and retrieval in hippocampal networks." acknowledged_ssus: - _id: ScienComp author: - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: Michael full_name: Frotscher, Michael last_name: Frotscher - 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: Guzmán J, Schlögl A, Frotscher M, Jonas PM. Synaptic mechanisms of pattern completion in the hippocampal CA3 network. Science. 2016;353(6304):1117-1123. doi:10.1126/science.aaf1836 apa: Guzmán, J., Schlögl, A., Frotscher, M., & Jonas, P. M. (2016). Synaptic mechanisms of pattern completion in the hippocampal CA3 network. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aaf1836 chicago: Guzmán, José, Alois Schlögl, Michael Frotscher, and Peter M Jonas. “Synaptic Mechanisms of Pattern Completion in the Hippocampal CA3 Network.” Science. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aaf1836. ieee: J. Guzmán, A. Schlögl, M. Frotscher, and P. M. Jonas, “Synaptic mechanisms of pattern completion in the hippocampal CA3 network,” Science, vol. 353, no. 6304. American Association for the Advancement of Science, pp. 1117–1123, 2016. ista: Guzmán J, Schlögl A, Frotscher M, Jonas PM. 2016. Synaptic mechanisms of pattern completion in the hippocampal CA3 network. Science. 353(6304), 1117–1123. mla: Guzmán, José, et al. “Synaptic Mechanisms of Pattern Completion in the Hippocampal CA3 Network.” Science, vol. 353, no. 6304, American Association for the Advancement of Science, 2016, pp. 1117–23, doi:10.1126/science.aaf1836. short: J. Guzmán, A. Schlögl, M. Frotscher, P.M. Jonas, Science 353 (2016) 1117–1123. date_created: 2018-12-11T11:51:31Z date_published: 2016-09-09T00:00:00Z date_updated: 2021-01-12T06:50:04Z day: '09' ddc: - '570' department: - _id: ScienComp - _id: PeJo doi: 10.1126/science.aaf1836 ec_funded: 1 file: - access_level: open_access checksum: 89caefa4e181424cbf0aecc835fcc5ec content_type: application/pdf creator: system date_created: 2018-12-12T10:12:27Z date_updated: 2020-07-14T12:44:46Z file_id: '4945' file_name: IST-2017-823-v1+1_aaf1836_CombinedPDF_v2-1.pdf file_size: 19408143 relation: main_file file_date_updated: 2020-07-14T12:44:46Z has_accepted_license: '1' intvolume: ' 353' issue: '6304' language: - iso: eng month: '09' oa: 1 oa_version: Preprint page: 1117 - 1123 project: - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '5899' pubrep_id: '823' quality_controlled: '1' scopus_import: 1 status: public title: Synaptic mechanisms of pattern completion in the hippocampal CA3 network type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 353 year: '2016' ... --- _id: '1435' abstract: - lang: eng text: ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer's disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states. article_number: '1207393' author: - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán - first_name: Zoltan full_name: Gerevich, Zoltan last_name: Gerevich citation: ama: 'Guzmán J, Gerevich Z. P2Y receptors in synaptic transmission and plasticity: Therapeutic potential in cognitive dysfunction. Neural Plasticity. 2016;2016. doi:10.1155/2016/1207393' apa: 'Guzmán, J., & Gerevich, Z. (2016). P2Y receptors in synaptic transmission and plasticity: Therapeutic potential in cognitive dysfunction. Neural Plasticity. Hindawi Publishing Corporation. https://doi.org/10.1155/2016/1207393' chicago: 'Guzmán, José, and Zoltan Gerevich. “P2Y Receptors in Synaptic Transmission and Plasticity: Therapeutic Potential in Cognitive Dysfunction.” Neural Plasticity. Hindawi Publishing Corporation, 2016. https://doi.org/10.1155/2016/1207393.' ieee: 'J. Guzmán and Z. Gerevich, “P2Y receptors in synaptic transmission and plasticity: Therapeutic potential in cognitive dysfunction,” Neural Plasticity, vol. 2016. Hindawi Publishing Corporation, 2016.' ista: 'Guzmán J, Gerevich Z. 2016. P2Y receptors in synaptic transmission and plasticity: Therapeutic potential in cognitive dysfunction. Neural Plasticity. 2016, 1207393.' mla: 'Guzmán, José, and Zoltan Gerevich. “P2Y Receptors in Synaptic Transmission and Plasticity: Therapeutic Potential in Cognitive Dysfunction.” Neural Plasticity, vol. 2016, 1207393, Hindawi Publishing Corporation, 2016, doi:10.1155/2016/1207393.' short: J. Guzmán, Z. Gerevich, Neural Plasticity 2016 (2016). date_created: 2018-12-11T11:52:00Z date_published: 2016-01-01T00:00:00Z date_updated: 2021-01-12T06:50:43Z day: '01' ddc: - '570' department: - _id: PeJo doi: 10.1155/2016/1207393 file: - access_level: open_access checksum: 8dc5c2f3d44d4775a6e7e3edb0d7a0da content_type: application/pdf creator: system date_created: 2018-12-12T10:09:17Z date_updated: 2020-07-14T12:44:54Z file_id: '4740' file_name: IST-2016-580-v1+1_1207393.pdf file_size: 1395180 relation: main_file file_date_updated: 2020-07-14T12:44:54Z has_accepted_license: '1' intvolume: ' 2016' language: - iso: eng month: '01' oa: 1 oa_version: Published Version publication: Neural Plasticity publication_status: published publisher: Hindawi Publishing Corporation publist_id: '5762' pubrep_id: '580' quality_controlled: '1' scopus_import: 1 status: public title: 'P2Y receptors in synaptic transmission and plasticity: Therapeutic potential in cognitive dysfunction' 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 2016 year: '2016' ... --- _id: '12903' article_processing_charge: No author: - first_name: Alois full_name: Schlögl, Alois id: 45BF87EE-F248-11E8-B48F-1D18A9856A87 last_name: Schlögl orcid: 0000-0002-5621-8100 - first_name: Stephan full_name: Stadlbauer, Stephan id: 4D0BC184-F248-11E8-B48F-1D18A9856A87 last_name: Stadlbauer citation: ama: 'Schlögl A, Stadlbauer S. High performance computing at IST Austria: Modelling the human hippocampus. In: AHPC16 - Austrian HPC Meeting 2016. VSC - Vienna Scientific Cluster; 2016:37.' apa: 'Schlögl, A., & Stadlbauer, S. (2016). High performance computing at IST Austria: Modelling the human hippocampus. In AHPC16 - Austrian HPC Meeting 2016 (p. 37). Grundlsee, Austria: VSC - Vienna Scientific Cluster.' chicago: 'Schlögl, Alois, and Stephan Stadlbauer. “High Performance Computing at IST Austria: Modelling the Human Hippocampus.” In AHPC16 - Austrian HPC Meeting 2016, 37. VSC - Vienna Scientific Cluster, 2016.' ieee: 'A. Schlögl and S. Stadlbauer, “High performance computing at IST Austria: Modelling the human hippocampus,” in AHPC16 - Austrian HPC Meeting 2016, Grundlsee, Austria, 2016, p. 37.' ista: 'Schlögl A, Stadlbauer S. 2016. High performance computing at IST Austria: Modelling the human hippocampus. AHPC16 - Austrian HPC Meeting 2016. AHPC: Austrian HPC Meeting, 37.' mla: 'Schlögl, Alois, and Stephan Stadlbauer. “High Performance Computing at IST Austria: Modelling the Human Hippocampus.” AHPC16 - Austrian HPC Meeting 2016, VSC - Vienna Scientific Cluster, 2016, p. 37.' short: A. Schlögl, S. Stadlbauer, in:, AHPC16 - Austrian HPC Meeting 2016, VSC - Vienna Scientific Cluster, 2016, p. 37. conference: end_date: 2016-02-24 location: Grundlsee, Austria name: 'AHPC: Austrian HPC Meeting' start_date: 2016-02-22 date_created: 2023-05-05T12:54:47Z date_published: 2016-02-24T00:00:00Z date_updated: 2023-05-16T07:15:14Z day: '24' ddc: - '000' department: - _id: ScienComp - _id: PeJo file: - access_level: open_access checksum: 4a7b00362e81358d568f5e216fa03c3e content_type: application/pdf creator: dernst date_created: 2023-05-16T07:03:56Z date_updated: 2023-05-16T07:03:56Z file_id: '12968' file_name: 2016_AHPC_Schloegl.pdf file_size: 1073523 relation: main_file success: 1 file_date_updated: 2023-05-16T07:03:56Z has_accepted_license: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://vsc.ac.at/fileadmin/user_upload/vsc/conferences/ahpc16/BOOKLET_AHPC16.pdf month: '02' oa: 1 oa_version: Published Version page: '37' publication: AHPC16 - Austrian HPC Meeting 2016 publication_status: published publisher: VSC - Vienna Scientific Cluster quality_controlled: '1' status: public title: 'High performance computing at IST Austria: Modelling the human hippocampus' type: conference_abstract user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2016' ... --- _id: '1432' abstract: - lang: eng text: CA3–CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at CA3–CA3 synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs) and action potentials (APs) induces long-term potentiation (LTP), independent of temporal order. The STDP curve is symmetric and broad (half-width ~150 ms). Consistent with these STDP induction properties, AP–EPSP sequences lead to supralinear summation of spine [Ca2+] transients. Furthermore, afterdepolarizations (ADPs) following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and EPSPs summate with dendritic ADPs. In autoassociative network models, storage and recall are more robust with symmetric than with asymmetric STDP rules. Thus, a specialized STDP induction rule allows reliable storage and recall of information in the hippocampal CA3 network. acknowledgement: 'We thank Jozsef Csicsvari and Nelson Spruston for critically reading the manuscript. We also thank A. Schlögl for programming, F. Marr for technical assistance and E. Kramberger for manuscript editing. ' article_number: '11552' author: - first_name: Rajiv Kumar full_name: Mishra, Rajiv Kumar id: 46CB58F2-F248-11E8-B48F-1D18A9856A87 last_name: Mishra - first_name: Sooyun full_name: Kim, Sooyun id: 394AB1C8-F248-11E8-B48F-1D18A9856A87 last_name: Kim - first_name: José full_name: Guzmán, José id: 30CC5506-F248-11E8-B48F-1D18A9856A87 last_name: Guzmán orcid: 0000-0003-2209-5242 - 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: Mishra RK, Kim S, Guzmán J, Jonas PM. Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks. Nature Communications. 2016;7. doi:10.1038/ncomms11552 apa: Mishra, R. K., Kim, S., Guzmán, J., & Jonas, P. M. (2016). Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms11552 chicago: Mishra, Rajiv Kumar, Sooyun Kim, José Guzmán, and Peter M Jonas. “Symmetric Spike Timing-Dependent Plasticity at CA3–CA3 Synapses Optimizes Storage and Recall in Autoassociative Networks.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms11552. ieee: R. K. Mishra, S. Kim, J. Guzmán, and P. M. Jonas, “Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks,” Nature Communications, vol. 7. Nature Publishing Group, 2016. ista: Mishra RK, Kim S, Guzmán J, Jonas PM. 2016. Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks. Nature Communications. 7, 11552. mla: Mishra, Rajiv Kumar, et al. “Symmetric Spike Timing-Dependent Plasticity at CA3–CA3 Synapses Optimizes Storage and Recall in Autoassociative Networks.” Nature Communications, vol. 7, 11552, Nature Publishing Group, 2016, doi:10.1038/ncomms11552. short: R.K. Mishra, S. Kim, J. Guzmán, P.M. Jonas, Nature Communications 7 (2016). date_created: 2018-12-11T11:51:59Z date_published: 2016-05-13T00:00:00Z date_updated: 2023-09-07T11:55:25Z day: '13' ddc: - '570' department: - _id: PeJo doi: 10.1038/ncomms11552 ec_funded: 1 file: - access_level: open_access checksum: 7e84d0392348c874d473b62f1042de22 content_type: application/pdf creator: system date_created: 2018-12-12T10:18:33Z date_updated: 2020-07-14T12:44:53Z file_id: '5355' file_name: IST-2016-582-v1+1_ncomms11552.pdf file_size: 4510512 relation: main_file file_date_updated: 2020-07-14T12:44:53Z has_accepted_license: '1' intvolume: ' 7' language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 25C26B1E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P24909-B24 name: Mechanisms of transmitter release at GABAergic synapses - _id: 25C0F108-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '268548' name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons publication: Nature Communications publication_status: published publisher: Nature Publishing Group publist_id: '5766' pubrep_id: '582' quality_controlled: '1' related_material: record: - id: '1396' relation: dissertation_contains status: public scopus_import: 1 status: public title: Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 7 year: '2016' ... --- _id: '1396' abstract: - lang: eng text: CA3 pyramidal neurons are thought to pay a key role in memory storage and pattern completion by activity-dependent synaptic plasticity between CA3-CA3 recurrent excitatory synapses. To examine the induction rules of synaptic plasticity at CA3-CA3 synapses, we performed whole-cell patch-clamp recordings in acute hippocampal slices from rats (postnatal 21-24 days) at room temperature. Compound excitatory postsynaptic potentials (ESPSs) were recorded by tract stimulation in stratum oriens in the presence of 10 µM gabazine. High-frequency stimulation (HFS) induced N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP). Although LTP by HFS did not requier postsynaptic spikes, it was blocked by Na+-channel blockers suggesting that local active processes (e.g.) dendritic spikes) may contribute to LTP induction without requirement of a somatic action potential (AP). We next examined the properties of spike timing-dependent plasticity (STDP) at CA3-CA3 synapses. Unexpectedly, low-frequency pairing of EPSPs and backpropagated action potentialy (bAPs) induced LTP, independent of temporal order. The STDP curve was symmetric and broad, with a half-width of ~150 ms. Consistent with these specific STDP induction properties, post-presynaptic sequences led to a supralinear summation of spine [Ca2+] transients. Furthermore, in autoassociative network models, storage and recall was substantially more robust with symmetric than with asymmetric STDP rules. In conclusion, we found associative forms of LTP at CA3-CA3 recurrent collateral synapses with distinct induction rules. LTP induced by HFS may be associated with dendritic spikes. In contrast, low frequency pairing of pre- and postsynaptic activity induced LTP only if EPSP-AP were temporally very close. Together, these induction mechanisms of synaptiic plasticity may contribute to memory storage in the CA3-CA3 microcircuit at different ranges of activity. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Rajiv Kumar full_name: Mishra, Rajiv Kumar id: 46CB58F2-F248-11E8-B48F-1D18A9856A87 last_name: Mishra citation: ama: Mishra RK. Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus. 2016. apa: Mishra, R. K. (2016). Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus. Institute of Science and Technology Austria. chicago: Mishra, Rajiv Kumar. “Synaptic Plasticity Rules at CA3-CA3 Recurrent Synapses in Hippocampus.” Institute of Science and Technology Austria, 2016. ieee: R. K. Mishra, “Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus,” Institute of Science and Technology Austria, 2016. ista: Mishra RK. 2016. Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus. Institute of Science and Technology Austria. mla: Mishra, Rajiv Kumar. Synaptic Plasticity Rules at CA3-CA3 Recurrent Synapses in Hippocampus. Institute of Science and Technology Austria, 2016. short: R.K. Mishra, Synaptic Plasticity Rules at CA3-CA3 Recurrent Synapses in Hippocampus, Institute of Science and Technology Austria, 2016. date_created: 2018-12-11T11:51:46Z date_published: 2016-03-01T00:00:00Z date_updated: 2023-09-07T11:55:26Z day: '01' ddc: - '570' degree_awarded: PhD department: - _id: PeJo file: - access_level: closed checksum: 5a010a838faf040f7064f3cfb802f743 content_type: application/pdf creator: dernst date_created: 2019-08-09T12:14:46Z date_updated: 2020-07-14T12:44:48Z file_id: '6782' file_name: Thesis_Mishra_Rajiv (Final).pdf file_size: 2407572 relation: main_file - access_level: open_access checksum: 81b26d9ede92c99f1d8cc6fa1d04cbbb content_type: application/pdf creator: dernst date_created: 2021-02-22T11:48:44Z date_updated: 2021-02-22T11:48:44Z file_id: '9183' file_name: 2016_RajivMishra_Thesis.pdf file_size: 2407572 relation: main_file success: 1 file_date_updated: 2021-02-22T11:48:44Z has_accepted_license: '1' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: '83' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '5811' related_material: record: - id: '1432' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2016' ... --- _id: '1616' abstract: - lang: eng text: The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3–6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation. acknowledgement: "The authors thank Jose Guzman for critically reading prior versions of the manuscript. They also thank T. Asenov for\r\nengineering mechanical devices, A. Schlögl for efficient pro-gramming, F. Marr for technical assistance, and E. Kramberger for manuscript editing." article_processing_charge: No author: - first_name: Janina full_name: Kowalski, Janina id: 3F3CA136-F248-11E8-B48F-1D18A9856A87 last_name: Kowalski - first_name: Jian full_name: Gan, Jian id: 3614E438-F248-11E8-B48F-1D18A9856A87 last_name: Gan - 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: Alejandro full_name: Pernia-Andrade, Alejandro id: 36963E98-F248-11E8-B48F-1D18A9856A87 last_name: Pernia-Andrade citation: ama: Kowalski J, Gan J, Jonas PM, Pernia-Andrade A. Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats. Hippocampus. 2016;26(5):668-682. doi:10.1002/hipo.22550 apa: Kowalski, J., Gan, J., Jonas, P. M., & Pernia-Andrade, A. (2016). Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats. Hippocampus. Wiley. https://doi.org/10.1002/hipo.22550 chicago: Kowalski, Janina, Jian Gan, Peter M Jonas, and Alejandro Pernia-Andrade. “Intrinsic Membrane Properties Determine Hippocampal Differential Firing Pattern in Vivo in Anesthetized Rats.” Hippocampus. Wiley, 2016. https://doi.org/10.1002/hipo.22550. ieee: J. Kowalski, J. Gan, P. M. Jonas, and A. Pernia-Andrade, “Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats,” Hippocampus, vol. 26, no. 5. Wiley, pp. 668–682, 2016. ista: Kowalski J, Gan J, Jonas PM, Pernia-Andrade A. 2016. Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats. Hippocampus. 26(5), 668–682. mla: Kowalski, Janina, et al. “Intrinsic Membrane Properties Determine Hippocampal Differential Firing Pattern in Vivo in Anesthetized Rats.” Hippocampus, vol. 26, no. 5, Wiley, 2016, pp. 668–82, doi:10.1002/hipo.22550. short: J. Kowalski, J. Gan, P.M. Jonas, A. Pernia-Andrade, Hippocampus 26 (2016) 668–682. date_created: 2018-12-11T11:53:03Z date_published: 2016-05-01T00:00:00Z date_updated: 2023-10-17T10:02:02Z day: '01' ddc: - '570' department: - _id: PeJo doi: 10.1002/hipo.22550 file: - access_level: open_access checksum: 284b72b12fbe15474833ed3d4549f86b content_type: application/pdf creator: system date_created: 2018-12-12T10:13:47Z date_updated: 2020-07-14T12:45:07Z file_id: '5033' file_name: IST-2016-469-v1+1_Kowalski_et_al-Hippocampus.pdf file_size: 905348 relation: main_file file_date_updated: 2020-07-14T12:45:07Z has_accepted_license: '1' intvolume: ' 26' issue: '5' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 668 - 682 publication: Hippocampus publication_identifier: eissn: - 1098-1063 issn: - 1050-9631 publication_status: published publisher: Wiley publist_id: '5550' pubrep_id: '469' quality_controlled: '1' scopus_import: '1' status: public title: Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats 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: 26 year: '2016' ... --- _id: '1535' abstract: - lang: eng text: Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuronlike” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress. acknowledgement: This work was supported by the Italian MIUR (PRIN 2010/2011 project 2010JFYFY2) and the University of Torino. article_processing_charge: No article_type: original author: - 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: Andrea full_name: Marcantoni, Andrea last_name: Marcantoni - first_name: Emilio full_name: Carbone, Emilio last_name: Carbone citation: ama: Vandael DH, Marcantoni A, Carbone E. Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells. Current Molecular Pharmacology. 2015;8(2):149-161. doi:10.2174/1874467208666150507105443 apa: Vandael, D. H., Marcantoni, A., & Carbone, E. (2015). Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells. Current Molecular Pharmacology. Bentham Science Publishers. https://doi.org/10.2174/1874467208666150507105443 chicago: Vandael, David H, Andrea Marcantoni, and Emilio Carbone. “Cav1.3 Channels as Key Regulators of Neuron-like Firings and Catecholamine Release in Chromaffin Cells.” Current Molecular Pharmacology. Bentham Science Publishers, 2015. https://doi.org/10.2174/1874467208666150507105443. ieee: D. H. Vandael, A. Marcantoni, and E. Carbone, “Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells,” Current Molecular Pharmacology, vol. 8, no. 2. Bentham Science Publishers, pp. 149–161, 2015. ista: Vandael DH, Marcantoni A, Carbone E. 2015. Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells. Current Molecular Pharmacology. 8(2), 149–161. mla: Vandael, David H., et al. “Cav1.3 Channels as Key Regulators of Neuron-like Firings and Catecholamine Release in Chromaffin Cells.” Current Molecular Pharmacology, vol. 8, no. 2, Bentham Science Publishers, 2015, pp. 149–61, doi:10.2174/1874467208666150507105443. short: D.H. Vandael, A. Marcantoni, E. Carbone, Current Molecular Pharmacology 8 (2015) 149–161. date_created: 2018-12-11T11:52:35Z date_published: 2015-10-01T00:00:00Z date_updated: 2021-01-12T06:51:26Z day: '01' department: - _id: PeJo doi: 10.2174/1874467208666150507105443 external_id: pmid: - '25966692' intvolume: ' 8' issue: '2' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384372/ month: '10' oa: 1 oa_version: Submitted Version page: 149 - 161 pmid: 1 publication: Current Molecular Pharmacology publication_status: published publisher: Bentham Science Publishers publist_id: '5636' quality_controlled: '1' scopus_import: 1 status: public title: Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 8 year: '2015' ... --- _id: '1565' abstract: - lang: eng text: Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite-suppressing effect. Besides being expressed in the hypothalamus and hippocampus, leptin receptors (ObRs) are also present in chromaffin cells of the adrenal medulla. In the present study, we report the effect of leptin on mouse chromaffin cell (MCC) functionality, focusing on cell excitability and catecholamine secretion. Acute application of leptin (1 nm) on spontaneously firing MCCs caused a slowly developing membrane hyperpolarization followed by complete blockade of action potential (AP) firing. This inhibitory effect at rest was abolished by the BK channel blocker paxilline (1 μm), suggesting the involvement of BK potassium channels. Single-channel recordings in 'perforated microvesicles' confirmed that leptin increased BK channel open probability without altering its unitary conductance. BK channel up-regulation was associated with the phosphoinositide 3-kinase (PI3K) signalling cascade because the PI3K specific inhibitor wortmannin (100 nm) fully prevented BK current increase. We also tested the effect of leptin on evoked AP firing and Ca2+-driven exocytosis. Although leptin preserves well-adapted AP trains of lower frequency, APs are broader and depolarization-evoked exocytosis is increased as a result of the larger size of the ready-releasable pool and higher frequency of vesicle release. The kinetics and quantal size of single secretory events remained unaltered. Leptin had no effect on firing and secretion in db-/db- mice lacking the ObR gene, confirming its specificity. In conclusion, leptin exhibits a dual action on MCC activity. It dampens AP firing at rest but preserves AP firing and increases catecholamine secretion during sustained stimulation, highlighting the importance of the adipo-adrenal axis in the leptin-mediated increase of sympathetic tone and catecholamine release. acknowledgement: "This work was supported by the Compagnia di San Paolo Foundation ‘Neuroscience Program’ to VC and ‘Progetto di Ateneo 2011-13’ to EC.\r\nWe thank Dr Claudio Franchino for cell preparation and for providing excellent technical support." author: - first_name: Daniela full_name: Gavello, Daniela last_name: Gavello - 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: Sara full_name: Gosso, Sara last_name: Gosso - first_name: Emilio full_name: Carbone, Emilio last_name: Carbone - first_name: Valentina full_name: Carabelli, Valentina last_name: Carabelli citation: ama: Gavello D, Vandael DH, Gosso S, Carbone E, Carabelli V. Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells. Journal of Physiology. 2015;593(22):4835-4853. doi:10.1113/JP271078 apa: Gavello, D., Vandael, D. H., Gosso, S., Carbone, E., & Carabelli, V. (2015). Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells. Journal of Physiology. Wiley-Blackwell. https://doi.org/10.1113/JP271078 chicago: Gavello, Daniela, David H Vandael, Sara Gosso, Emilio Carbone, and Valentina Carabelli. “Dual Action of Leptin on Rest-Firing and Stimulated Catecholamine Release via Phosphoinositide 3-Kinase-Riven BK Channel up-Regulation in Mouse Chromaffin Cells.” Journal of Physiology. Wiley-Blackwell, 2015. https://doi.org/10.1113/JP271078. ieee: D. Gavello, D. H. Vandael, S. Gosso, E. Carbone, and V. Carabelli, “Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells,” Journal of Physiology, vol. 593, no. 22. Wiley-Blackwell, pp. 4835–4853, 2015. ista: Gavello D, Vandael DH, Gosso S, Carbone E, Carabelli V. 2015. Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells. Journal of Physiology. 593(22), 4835–4853. mla: Gavello, Daniela, et al. “Dual Action of Leptin on Rest-Firing and Stimulated Catecholamine Release via Phosphoinositide 3-Kinase-Riven BK Channel up-Regulation in Mouse Chromaffin Cells.” Journal of Physiology, vol. 593, no. 22, Wiley-Blackwell, 2015, pp. 4835–53, doi:10.1113/JP271078. short: D. Gavello, D.H. Vandael, S. Gosso, E. Carbone, V. Carabelli, Journal of Physiology 593 (2015) 4835–4853. date_created: 2018-12-11T11:52:45Z date_published: 2015-11-15T00:00:00Z date_updated: 2021-01-12T06:51:38Z day: '15' department: - _id: PeJo doi: 10.1113/JP271078 external_id: pmid: - '26282459' intvolume: ' 593' issue: '22' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650409/ month: '11' oa: 1 oa_version: Submitted Version page: 4835 - 4853 pmid: 1 publication: Journal of Physiology publication_status: published publisher: Wiley-Blackwell publist_id: '5606' quality_controlled: '1' scopus_import: 1 status: public title: Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 593 year: '2015' ... --- _id: '1580' abstract: - lang: eng text: Synapsins (Syns) are an evolutionarily conserved family of presynaptic proteins crucial for the fine-tuning of synaptic function. A large amount of experimental evidences has shown that Syns are involved in the development of epileptic phenotypes and several mutations in Syn genes have been associated with epilepsy in humans and animal models. Syn mutations induce alterations in circuitry and neurotransmitter release, differentially affecting excitatory and inhibitory synapses, thus causing an excitation/inhibition imbalance in network excitability toward hyperexcitability that may be a determinant with regard to the development of epilepsy. Another approach to investigate epileptogenic mechanisms is to understand how silencing Syn affects the cellular behavior of single neurons and is associated with the hyperexcitable phenotypes observed in epilepsy. Here, we examined the functional effects of antisense-RNA inhibition of Syn expression on individually identified and isolated serotonergic cells of the Helix land snail. We found that Helix synapsin silencing increases cell excitability characterized by a slightly depolarized resting membrane potential, decreases the rheobase, reduces the threshold for action potential (AP) firing and increases the mean and instantaneous firing rates, with respect to control cells. The observed increase of Ca2+ and BK currents in Syn-silenced cells seems to be related to changes in the shape of the AP waveform. These currents sustain the faster spiking in Syn-deficient cells by increasing the after hyperpolarization and limiting the Na+ and Ca2+ channel inactivation during repetitive firing. This in turn speeds up the depolarization phase by reaching the AP threshold faster. Our results provide evidence that Syn silencing increases intrinsic cell excitability associated with increased Ca2+ and Ca2+-dependent BK currents in the absence of excitatory or inhibitory inputs. article_processing_charge: No article_type: original author: - first_name: Oscar full_name: Brenes, Oscar last_name: Brenes - 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: Emilio full_name: Carbone, Emilio last_name: Carbone - first_name: Pier full_name: Montarolo, Pier last_name: Montarolo - first_name: Mirella full_name: Ghirardi, Mirella last_name: Ghirardi citation: ama: Brenes O, Vandael DH, Carbone E, Montarolo P, Ghirardi M. Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons. Neuroscience. 2015;311:430-443. doi:10.1016/j.neuroscience.2015.10.046 apa: Brenes, O., Vandael, D. H., Carbone, E., Montarolo, P., & Ghirardi, M. (2015). Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons. Neuroscience. Elsevier. https://doi.org/10.1016/j.neuroscience.2015.10.046 chicago: Brenes, Oscar, David H Vandael, Emilio Carbone, Pier Montarolo, and Mirella Ghirardi. “Knock-down of Synapsin Alters Cell Excitability and Action Potential Waveform by Potentiating BK and Voltage Gated Ca2 Currents in Helix Serotonergic Neurons.” Neuroscience. Elsevier, 2015. https://doi.org/10.1016/j.neuroscience.2015.10.046. ieee: O. Brenes, D. H. Vandael, E. Carbone, P. Montarolo, and M. Ghirardi, “Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons,” Neuroscience, vol. 311. Elsevier, pp. 430–443, 2015. ista: Brenes O, Vandael DH, Carbone E, Montarolo P, Ghirardi M. 2015. Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons. Neuroscience. 311, 430–443. mla: Brenes, Oscar, et al. “Knock-down of Synapsin Alters Cell Excitability and Action Potential Waveform by Potentiating BK and Voltage Gated Ca2 Currents in Helix Serotonergic Neurons.” Neuroscience, vol. 311, Elsevier, 2015, pp. 430–43, doi:10.1016/j.neuroscience.2015.10.046. short: O. Brenes, D.H. Vandael, E. Carbone, P. Montarolo, M. Ghirardi, Neuroscience 311 (2015) 430–443. date_created: 2018-12-11T11:52:50Z date_published: 2015-12-17T00:00:00Z date_updated: 2021-01-12T06:51:44Z day: '17' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.neuroscience.2015.10.046 file: - access_level: open_access checksum: af2c4c994718c7be417eba0dc746aac9 content_type: application/pdf creator: dernst date_created: 2020-05-15T06:50:20Z date_updated: 2020-07-14T12:45:02Z file_id: '7849' file_name: 2015_Neuroscience_Brenes.pdf file_size: 5563015 relation: main_file file_date_updated: 2020-07-14T12:45:02Z has_accepted_license: '1' intvolume: ' 311' language: - iso: eng month: '12' oa: 1 oa_version: Submitted Version page: 430 - 443 publication: Neuroscience publication_status: published publisher: Elsevier publist_id: '5591' quality_controlled: '1' scopus_import: 1 status: public title: Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons 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: 311 year: '2015' ... --- _id: '1615' abstract: - lang: eng text: Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among the most common genetic abnormalities associated with autism spectrum disorders, but little is known about the function of Neuroligin-4 and the consequences of its loss. We assessed synaptic and network characteristics in Neuroligin-4 knockout mice, focusing on the hippocampus as a model brain region with a critical role in cognition and memory, and found that Neuroligin-4 deletion causes subtle defects of the protein composition and function of GABAergic synapses in the hippocampal CA3 region. Interestingly, these subtle synaptic changes are accompanied by pronounced perturbations of γ-oscillatory network activity, which has been implicated in cognitive function and is altered in multiple psychiatric and neurodevelopmental disorders. Our data provide important insights into the mechanisms by which Neuroligin-4-dependent GABAergic synapses may contribute to autism phenotypes and indicate new strategies for therapeutic approaches. acknowledgement: This work was supported by the Max Planck Society (N.B. and H.E.), the European Commission (EU-AIMS FP7-115300, N.B. and H.E.; Marie Curie IRG, D.K.-B.), the German Research Foundation (CNMPB, N.B., H.E., and F.V.), the Alexander von Humboldt-Foundation (D.K.-B.), and the Austrian Fond zur Förderung der Wissenschaftlichen Forschung (P 24909-B24, P.J.). M.H. was a student of the doctoral program Molecular Physiology of the Brain. Dr. J.-M. Fritschy generously provided the GABAARγ2 antibody. We thank F. Benseler, I. Thanhäuser, D. Schwerdtfeger, A. Ronnenberg, and D. Winkler for valuable advice and excellent technical support. We are grateful to the staff at the animal facility of the Max Planck Institute of Experimental Medicine for mouse husbandry. author: - first_name: Matthieu full_name: Hammer, Matthieu last_name: Hammer - first_name: Dilja full_name: Krueger Burg, Dilja last_name: Krueger Burg - first_name: Liam full_name: Tuffy, Liam last_name: Tuffy - first_name: Benjamin full_name: Cooper, Benjamin last_name: Cooper - first_name: Holger full_name: Taschenberger, Holger last_name: Taschenberger - first_name: Sarit full_name: Goswami, Sarit id: 3A578F32-F248-11E8-B48F-1D18A9856A87 last_name: Goswami - first_name: Hannelore full_name: Ehrenreich, Hannelore last_name: Ehrenreich - 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: Frederique full_name: Varoqueaux, Frederique last_name: Varoqueaux - first_name: Jeong full_name: Rhee, Jeong last_name: Rhee - first_name: Nils full_name: Brose, Nils last_name: Brose citation: ama: Hammer M, Krueger Burg D, Tuffy L, et al. Perturbed hippocampal synaptic inhibition and γ-oscillations in a neuroligin-4 knockout mouse model of autism. Cell Reports. 2015;13(3):516-523. doi:10.1016/j.celrep.2015.09.011 apa: Hammer, M., Krueger Burg, D., Tuffy, L., Cooper, B., Taschenberger, H., Goswami, S., … Brose, N. (2015). Perturbed hippocampal synaptic inhibition and γ-oscillations in a neuroligin-4 knockout mouse model of autism. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2015.09.011 chicago: Hammer, Matthieu, Dilja Krueger Burg, Liam Tuffy, Benjamin Cooper, Holger Taschenberger, Sarit Goswami, Hannelore Ehrenreich, et al. “Perturbed Hippocampal Synaptic Inhibition and γ-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism.” Cell Reports. Cell Press, 2015. https://doi.org/10.1016/j.celrep.2015.09.011. ieee: M. Hammer et al., “Perturbed hippocampal synaptic inhibition and γ-oscillations in a neuroligin-4 knockout mouse model of autism,” Cell Reports, vol. 13, no. 3. Cell Press, pp. 516–523, 2015. ista: Hammer M, Krueger Burg D, Tuffy L, Cooper B, Taschenberger H, Goswami S, Ehrenreich H, Jonas PM, Varoqueaux F, Rhee J, Brose N. 2015. Perturbed hippocampal synaptic inhibition and γ-oscillations in a neuroligin-4 knockout mouse model of autism. Cell Reports. 13(3), 516–523. mla: Hammer, Matthieu, et al. “Perturbed Hippocampal Synaptic Inhibition and γ-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism.” Cell Reports, vol. 13, no. 3, Cell Press, 2015, pp. 516–23, doi:10.1016/j.celrep.2015.09.011. short: M. Hammer, D. Krueger Burg, L. Tuffy, B. Cooper, H. Taschenberger, S. Goswami, H. Ehrenreich, P.M. Jonas, F. Varoqueaux, J. Rhee, N. Brose, Cell Reports 13 (2015) 516–523. date_created: 2018-12-11T11:53:02Z date_published: 2015-10-20T00:00:00Z date_updated: 2021-01-12T06:52:01Z day: '20' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.celrep.2015.09.011 file: - access_level: open_access checksum: 44d30fbb543774b076b4938bd36af9d7 content_type: application/pdf creator: system date_created: 2018-12-12T10:13:23Z date_updated: 2020-07-14T12:45:07Z file_id: '5005' file_name: IST-2016-470-v1+1_1-s2.0-S2211124715010220-main.pdf file_size: 2314406 relation: main_file file_date_updated: 2020-07-14T12:45:07Z has_accepted_license: '1' intvolume: ' 13' issue: '3' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: 516 - 523 publication: Cell Reports publication_status: published publisher: Cell Press publist_id: '5551' pubrep_id: '470' quality_controlled: '1' scopus_import: 1 status: public title: Perturbed hippocampal synaptic inhibition and γ-oscillations in a neuroligin-4 knockout mouse model of autism 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: 13 year: '2015' ...