[{"related_material":{"record":[{"relation":"earlier_version","id":"18688","status":"public"}]},"language":[{"iso":"eng"}],"license":"https://creativecommons.org/licenses/by/4.0/","title":"Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory","volume":188,"file_date_updated":"2025-01-27T08:46:33Z","date_created":"2025-01-26T23:01:49Z","abstract":[{"text":"Our brain has remarkable computational power, generating sophisticated behaviors, storing memories over an individual’s lifetime, and producing higher cognitive functions. However, little of our neuroscience knowledge covers the human brain. Is this organ truly unique, or is it a scaled version of the extensively studied rodent brain? Combining multicellular patch-clamp recording with expansion-based superresolution microscopy and full-scale modeling, we determined the cellular and microcircuit properties of the human hippocampal CA3 region, a fundamental circuit for memory storage. In contrast to neocortical networks, human hippocampal CA3 displayed sparse connectivity, providing a circuit architecture that maximizes associational power. Human synapses showed unique reliability, high precision, and long integration times, exhibiting both species- and circuit-specific properties. Together with expanded neuronal numbers, these circuit characteristics greatly enhanced the memory storage capacity of CA3. Our results reveal distinct microcircuit properties of the human hippocampus and begin to unravel the inner workings of our most complex organ. ","lang":"eng"}],"day":"23","scopus_import":"1","isi":1,"pmid":1,"quality_controlled":"1","author":[{"id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","first_name":"Jake","last_name":"Watson","orcid":"0000-0002-8698-3823"},{"last_name":"Vargas Barroso","first_name":"Victor M","full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Morse","id":"ceb89ae7-dc8d-11ea-abe3-da3301d0eab4","full_name":"Morse, Rebecca","first_name":"Rebecca"},{"full_name":"Navas Olivé, Andrea C","first_name":"Andrea C","id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","orcid":"0000-0002-9280-8597","last_name":"Navas Olivé"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli","orcid":"0000-0002-7667-6854"},{"last_name":"Danzl","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","first_name":"Johann G"},{"full_name":"Tomschik, Matthias","first_name":"Matthias","last_name":"Tomschik"},{"full_name":"Rössler, Karl","first_name":"Karl","last_name":"Rössler"},{"first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"page":"501-514.e18","_id":"18879","doi":"10.1016/j.cell.2024.11.022","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","call_identifier":"H2020"},{"grant_number":"26137","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232","call_identifier":"FWF","name":"Molecular Drug Targets"},{"name":"Synaptic networks of human brain","grant_number":"PAT 4178023","_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e"},{"_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A","name":"NOMIS Fellowship Program"}],"publication":"Cell","type":"journal_article","ddc":["570"],"external_id":{"isi":["001408395600001"],"pmid":["39667938"]},"citation":{"short":"J. Watson, V.M. Vargas Barroso, R. Morse, A.C. Navas Olivé, M. Tavakoli, J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, Cell 188 (2025) 501–514.e18.","chicago":"Watson, Jake, Victor M Vargas Barroso, Rebecca Morse, Andrea C Navas Olivé, Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>Cell</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">https://doi.org/10.1016/j.cell.2024.11.022</a>.","ista":"Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG, Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18.","ama":"Watson J, Vargas Barroso VM, Morse R, et al. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>Cell</i>. 2025;188(2):501-514.e18. doi:<a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">10.1016/j.cell.2024.11.022</a>","apa":"Watson, J., Vargas Barroso, V. M., Morse, R., Navas Olivé, A. C., Tavakoli, M., Danzl, J. G., … Jonas, P. M. (2025). Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">https://doi.org/10.1016/j.cell.2024.11.022</a>","mla":"Watson, Jake, et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>Cell</i>, vol. 188, no. 2, Elsevier, 2025, p. 501–514.e18, doi:<a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">10.1016/j.cell.2024.11.022</a>.","ieee":"J. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory,” <i>Cell</i>, vol. 188, no. 2. Elsevier, p. 501–514.e18, 2025."},"acknowledgement":"We thank Florian Marr for excellent technical assistance, Christina Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor Asenov for development of the transportation box for human brain tissue, Tim Vogels for guidance on simulations, Marcus Huber for mathematical advice, Walter Kaufmann for assistance with handling frozen tissue, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA, and we are grateful for assistance from Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Lab Support Facility, Miba Machine Shop, and Scientific Computing. We are particularly grateful to the patient donors for their support of this project and also acknowledge the excellent support of the Medical University of Vienna Department of Neurosurgery staff; Romana Hoeftberger and the Division of Neuropathology and Neurochemistry; Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology; and Christoph Baumgartner, Martha Feucht, and Ekaterina Pataraia for their clinical care of the patients included in this study. We thank Laura Jonkman, the NABCA biobank, and postmortem brain sample donors for their support of this research. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (advanced grant no. 692692 to P.J. and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund (FWF; grant PAT 4178023 to P.J. and grant DK W1232 to M.R.T. and J.G.D.), the Austrian Academy of Sciences (DOC fellowship 26137 to M.R.T.), and a NOMIS-ISTA fellowship (to A.N.-O.).","intvolume":"       188","oa":1,"article_processing_charge":"Yes (via OA deal)","department":[{"_id":"JoDa"},{"_id":"PeJo"},{"_id":"GradSch"}],"date_updated":"2026-04-14T08:34:32Z","publication_status":"published","date_published":"2025-01-23T00:00:00Z","month":"01","article_type":"original","publisher":"Elsevier","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"ec_funded":1,"year":"2025","status":"public","issue":"2","corr_author":"1","has_accepted_license":"1","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"OA_place":"publisher","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","file":[{"date_updated":"2025-01-27T08:46:33Z","file_size":14082343,"content_type":"application/pdf","checksum":"d5a818edc32d249cdf75e1bb5b70a4b7","access_level":"open_access","creator":"dernst","success":1,"file_id":"18884","date_created":"2025-01-27T08:46:33Z","file_name":"2025_Cell_Watson.pdf","relation":"main_file"}],"OA_type":"hybrid","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"}},{"isi":1,"scopus_import":"1","file_date_updated":"2025-08-04T06:53:07Z","volume":44,"DOAJ_listed":"1","title":"Cell-specific wiring routes information flow through hippocampal CA3","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"The hippocampus, critical for learning and memory, is dogmatically described as a trisynaptic circuit where dentate gyrus granule cells (GCs), CA3 pyramidal neurons (PNs), and CA1 PNs are serially connected. However, CA3 also forms an autoassociative network, and its PNs have diverse morphologies, intrinsic properties, and GC input levels. How PN subtypes compose this recurrent network is unknown. To determine the synaptic arrangement of identified CA3 PNs, we combine multicellular patch-clamp recording and post hoc morphological analysis in mouse hippocampal slices. PNs can be divided into distinct “superficial” and “deep” subclasses, the latter including previously reported “athorny” cells. Subclasses have distinct input-output transformations and asymmetric connectivity, which is more abundant from superficial to deep PNs, splitting CA3 locally into two parallel recurrent networks. Coincident spontaneous inhibition occurs frequently within but not between subclasses, implying subclass-specific inhibitory innervation. Our results suggest two separately controlled sublayers for parallel information processing in hippocampal CA3."}],"day":"01","date_created":"2025-08-03T22:01:30Z","publication":"Cell Reports","type":"journal_article","intvolume":"        44","acknowledgement":"We thank Andrea Navas-Olive and Rebecca J. Morse-Mora for critically reading an earlier version of the manuscript. We also thank Florian Marr and Christina Altmutter for excellent technical assistance, Alois Schlögl for programming and data-handling assistance, Todor Asenov for technical support, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA. We are particularly grateful for assistance from the Imaging and Optics Facility, Preclinical Facility, Lab Support Facility, and Miba Machine Shop. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692 to P.J., Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W., and an ISTplus Fellowship through Marie Skłodowska-Curie grant agreement no. 754411 to V.V.-B.), the Austrian Science Fund (P 36232-B, PAT 4178023, and Cluster of Excellence 10.55776/COE16 to P.J.), and a CONACyT fellowship (289638 to V.V.-B.) and was supported by a non-stipendiary EMBO fellowship (ALTF 756–2020 to J.F.W.).","citation":{"mla":"Watson, Jake, et al. “Cell-Specific Wiring Routes Information Flow through Hippocampal CA3.” <i>Cell Reports</i>, vol. 44, no. 8, 116080, Elsevier, 2025, doi:<a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">10.1016/j.celrep.2025.116080</a>.","ieee":"J. Watson, V. M. Vargas Barroso, and P. M. Jonas, “Cell-specific wiring routes information flow through hippocampal CA3,” <i>Cell Reports</i>, vol. 44, no. 8. Elsevier, 2025.","ama":"Watson J, Vargas Barroso VM, Jonas PM. Cell-specific wiring routes information flow through hippocampal CA3. <i>Cell Reports</i>. 2025;44(8). doi:<a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">10.1016/j.celrep.2025.116080</a>","apa":"Watson, J., Vargas Barroso, V. M., &#38; Jonas, P. M. (2025). Cell-specific wiring routes information flow through hippocampal CA3. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">https://doi.org/10.1016/j.celrep.2025.116080</a>","ista":"Watson J, Vargas Barroso VM, Jonas PM. 2025. Cell-specific wiring routes information flow through hippocampal CA3. Cell Reports. 44(8), 116080.","short":"J. Watson, V.M. Vargas Barroso, P.M. Jonas, Cell Reports 44 (2025).","chicago":"Watson, Jake, Victor M Vargas Barroso, and Peter M Jonas. “Cell-Specific Wiring Routes Information Flow through Hippocampal CA3.” <i>Cell Reports</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">https://doi.org/10.1016/j.celrep.2025.116080</a>."},"ddc":["570"],"external_id":{"isi":["001544472300002"]},"author":[{"orcid":"0000-0002-8698-3823","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"last_name":"Vargas Barroso","first_name":"Victor M","full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jonas","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M"}],"quality_controlled":"1","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","call_identifier":"H2020"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232"},{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"doi":"10.1016/j.celrep.2025.116080","_id":"20099","PlanS_conform":"1","date_published":"2025-08-01T00:00:00Z","month":"08","article_type":"original","date_updated":"2025-09-30T14:12:02Z","publication_status":"published","ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"publisher":"Elsevier","oa":1,"article_number":"116080","department":[{"_id":"PeJo"}],"article_processing_charge":"Yes","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","OA_place":"publisher","publication_identifier":{"issn":["2639-1856"],"eissn":["2211-1247"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"OA_type":"gold","file":[{"relation":"main_file","file_name":"2025_CellReports_Watson.pdf","date_created":"2025-08-04T06:53:07Z","file_id":"20106","success":1,"creator":"dernst","content_type":"application/pdf","checksum":"556ff9760661ecd23949d75031043b1f","access_level":"open_access","file_size":27695214,"date_updated":"2025-08-04T06:53:07Z"}],"oa_version":"Published Version","status":"public","year":"2025","issue":"8","has_accepted_license":"1","corr_author":"1"},{"isi":1,"scopus_import":"1","pmid":1,"volume":42,"file_date_updated":"2025-01-09T07:48:01Z","language":[{"iso":"eng"}],"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}],"record":[{"status":"deleted","relation":"dissertation_contains","id":"18660"},{"id":"13126","relation":"research_data","status":"public"},{"id":"18674","relation":"dissertation_contains","status":"public"}]},"title":"Imaging brain tissue architecture across millimeter to nanometer scales","date_created":"2023-09-03T22:01:15Z","abstract":[{"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.","lang":"eng"}],"day":"01","type":"journal_article","publication":"Nature Biotechnology","intvolume":"        42","ddc":["570"],"external_id":{"pmid":["37653226"],"isi":["001065254200001"]},"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.).","citation":{"apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2024;42:1051-1064. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, vol. 42, Springer Nature, 2024, pp. 1051–64, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>.","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>, vol. 42. Springer Nature, pp. 1051–1064, 2024.","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.” <i>Nature Biotechnology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>.","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 42 (2024) 1051–1064.","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. 2024. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 42, 1051–1064."},"author":[{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","first_name":"Julia M","last_name":"Michalska","orcid":"0000-0003-3862-1235"},{"last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia"},{"orcid":"0000-0002-2340-7431","last_name":"Velicky","first_name":"Philipp","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","full_name":"Korinkova, Hana","last_name":"Korinkova"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","first_name":"Jake","last_name":"Watson","orcid":"0000-0002-8698-3823"},{"last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","first_name":"Alban"},{"orcid":"0000-0003-1216-9105","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","full_name":"Amberg, Nicole","last_name":"Amberg","orcid":"0000-0002-3183-8207"},{"orcid":"0000-0003-2356-9403","last_name":"Venturino","full_name":"Venturino, Alessandro","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Roessler","full_name":"Roessler, Karl","first_name":"Karl"},{"last_name":"Czech","first_name":"Thomas","full_name":"Czech, Thomas"},{"full_name":"Höftberger, Romana","first_name":"Romana","last_name":"Höftberger"},{"orcid":"0000-0001-8635-0877","last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","first_name":"Gaia"},{"last_name":"Jonas","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973"}],"page":"1051-1064","quality_controlled":"1","project":[{"name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Drug Targets","grant_number":"W1232","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"grant_number":"LS18-022","name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","call_identifier":"H2020","name":"International IST Doctoral Program"},{"call_identifier":"H2020","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"_id":"14257","doi":"10.1038/s41587-023-01911-8","date_updated":"2026-04-14T08:34:35Z","publication_status":"published","article_type":"original","date_published":"2024-07-01T00:00:00Z","month":"07","ec_funded":1,"publisher":"Springer Nature","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"oa":1,"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"article_processing_charge":"Yes (in subscription journal)","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"OA_place":"publisher","OA_type":"hybrid","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"oa_version":"Published Version","file":[{"checksum":"57d5fafb16f02dcb9f7dddb1bd7e2a71","content_type":"application/pdf","file_size":26065165,"access_level":"open_access","creator":"dernst","success":1,"date_updated":"2025-01-09T07:48:01Z","date_created":"2025-01-09T07:48:01Z","file_name":"2024_NatureBiotech_Michalska.pdf","relation":"main_file","file_id":"18784"}],"year":"2024","status":"public","corr_author":"1","has_accepted_license":"1"},{"publication":"Science","type":"journal_article","intvolume":"       383","external_id":{"isi":["001216996700015"],"pmid":["38452088"]},"citation":{"mla":"Vandael, David H., and Peter M. Jonas. “Structure, Biophysics, and Circuit Function of a ‘Giant’ Cortical Presynaptic Terminal.” <i>Science</i>, vol. 383, no. 6687, AAAS, 2024, p. eadg6757, doi:<a href=\"https://doi.org/10.1126/science.adg6757\">10.1126/science.adg6757</a>.","ieee":"D. H. Vandael and P. M. Jonas, “Structure, biophysics, and circuit function of a ‘giant’ cortical presynaptic terminal,” <i>Science</i>, vol. 383, no. 6687. AAAS, p. eadg6757, 2024.","apa":"Vandael, D. H., &#38; Jonas, P. M. (2024). Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal. <i>Science</i>. AAAS. <a href=\"https://doi.org/10.1126/science.adg6757\">https://doi.org/10.1126/science.adg6757</a>","ama":"Vandael DH, Jonas PM. Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal. <i>Science</i>. 2024;383(6687):eadg6757. doi:<a href=\"https://doi.org/10.1126/science.adg6757\">10.1126/science.adg6757</a>","ista":"Vandael DH, Jonas PM. 2024. Structure, biophysics, and circuit function of a ‘giant’ cortical presynaptic terminal. Science. 383(6687), eadg6757.","chicago":"Vandael, David H, and Peter M Jonas. “Structure, Biophysics, and Circuit Function of a ‘Giant’ Cortical Presynaptic Terminal.” <i>Science</i>. AAAS, 2024. <a href=\"https://doi.org/10.1126/science.adg6757\">https://doi.org/10.1126/science.adg6757</a>.","short":"D.H. Vandael, P.M. Jonas, Science 383 (2024) eadg6757."},"acknowledgement":"We thank previous students, postdocs, and collaborators, particularly J. Geiger, and (in alphabetical order) H. Alle, J. Bischofberger, C. Borges-Merjane, D. Engel, M. Frotscher, S. Hallermann, M. Heckmann, S. Jamrichova, O. Kim, L. Li, K. Lichter, P. Lin, J. Lübke, Y. Okamoto, C. Pawlu, C. Schmidt-Hieber, N. Spruston, and N. Vyleta for their outstanding experimental contributions. We also thank P. Castillo, J. Geiger, T. Sakaba, S. Siegert, T. Vogels, and J. Watson for critically reading the manuscript, E. Kralli-Beller for text editing, and J. Malikovic and L. Slomianka for useful discussions. We apologize that, due to space constraints, not all relevant papers could be cited.\r\nThis project was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, AdG “GIANTSYN”) and the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein Award; P 36232-B, stand-alone grant), both to P.J.","author":[{"last_name":"Vandael","orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","full_name":"Vandael, David H","first_name":"David H"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"page":"eadg6757","quality_controlled":"1","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"grant_number":"Z00312","call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"}],"_id":"15117","doi":"10.1126/science.adg6757","isi":1,"scopus_import":"1","pmid":1,"volume":383,"language":[{"iso":"eng"}],"title":"Structure, biophysics, and circuit function of a \"giant\" cortical presynaptic terminal","date_created":"2024-03-17T23:00:57Z","abstract":[{"lang":"eng","text":"The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and “flash-and-freeze” electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations."}],"day":"08","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","publication_identifier":{"eissn":["1095-9203"]},"oa_version":"None","status":"public","year":"2024","issue":"6687","corr_author":"1","publication_status":"published","date_updated":"2025-09-04T13:04:34Z","date_published":"2024-03-08T00:00:00Z","month":"03","article_type":"review","ec_funded":1,"publisher":"AAAS","department":[{"_id":"PeJo"}],"article_processing_charge":"No"},{"_id":"18603","doi":"10.1371/journal.pbio.3002879","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"grant_number":"Z00312","call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"name":"Structural & functional basis of presynaptic plasticity","grant_number":"I06166","_id":"b1b85715-d554-11ed-a5ad-84a07fc9f18e"},{"name":"Zellkommunikation in Gesundheit und Krankheit","call_identifier":"FWF","grant_number":"W01205","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"FWF Open Access Fund","_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1"}],"quality_controlled":"1","author":[{"last_name":"Kim","orcid":"0000-0003-2344-1039","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","full_name":"Kim, Olena","first_name":"Olena"},{"last_name":"Okamoto","orcid":"0000-0003-0408-6094","id":"3337E116-F248-11E8-B48F-1D18A9856A87","first_name":"Yuji","full_name":"Okamoto, Yuji"},{"last_name":"Kaufmann","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","full_name":"Kaufmann, Walter","first_name":"Walter"},{"full_name":"Brose, Nils","first_name":"Nils","last_name":"Brose"},{"last_name":"Shigemoto","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi"},{"full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"ddc":["570"],"external_id":{"pmid":["39556620"],"isi":["001358568700003"]},"acknowledgement":"We thank Carolina Borges-Merjane, Jing-Jing Chen, Katharina Lichter, and Samuel Young for critically reading the manuscript; the Electron Microscopy Facility of ISTA, in particular Vanessa Zheden, for extensive support, advice, and experimental assistance; the Preclinical Facility of ISTA, in particular Victoria Wimmer and Michael Schunn, for experimental assistance; Florian Marr and Christina Altmutter for technical support; Alois Schlögl for help with analysis; and Eleftheria Kralli-Beller for manuscript editing. We also thank Cordelia Imig for providing Munc13-1cKO-Munc13-2/3(−/−) mutant mice. Part of the work has been published in O.K.’s thesis in partial fulfillment of the requirements for the degree of Doctor of Philosophy.\r\nThis project received funding from the European Research Council and European Union’s Horizon 2020 research and innovation programme (ERC 692692 to P.J.; https://cordis.europa.eu/project/id/692692/de) and from the Fond zur Förderung der Wissenschaftlichen Forschung (Z312-B27 Wittgenstein award to P.J., https://www.fwf.ac.at/en/funding/portfolio/projects/fwf-wittgenstein-award; W1205-B09 and P36232-B to P.J., https://www.fwf.ac.at/en/funding; I6166-B to R.S.; https://www.fwf.ac.at/en/funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","citation":{"ieee":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,” <i>PLoS Biology</i>, vol. 22, no. 11. Public Library of Science, 2024.","mla":"Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” <i>PLoS Biology</i>, vol. 22, no. 11, e3002879, Public Library of Science, 2024, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002879\">10.1371/journal.pbio.3002879</a>.","apa":"Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., &#38; Jonas, P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3002879\">https://doi.org/10.1371/journal.pbio.3002879</a>","ama":"Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. <i>PLoS Biology</i>. 2024;22(11). doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002879\">10.1371/journal.pbio.3002879</a>","ista":"Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. 22(11), e3002879.","chicago":"Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto, and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” <i>PLoS Biology</i>. Public Library of Science, 2024. <a href=\"https://doi.org/10.1371/journal.pbio.3002879\">https://doi.org/10.1371/journal.pbio.3002879</a>.","short":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS Biology 22 (2024)."},"intvolume":"        22","type":"journal_article","publication":"PLoS Biology","date_created":"2024-12-01T23:01:54Z","abstract":[{"lang":"eng","text":"It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse."}],"day":"18","related_material":{"record":[{"id":"18296","relation":"research_data","status":"public"}]},"language":[{"iso":"eng"}],"DOAJ_listed":"1","title":"Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons","volume":22,"file_date_updated":"2024-12-03T08:56:53Z","pmid":1,"scopus_import":"1","isi":1,"corr_author":"1","has_accepted_license":"1","status":"public","year":"2024","issue":"11","oa_version":"Published Version","file":[{"date_updated":"2024-12-03T08:56:53Z","creator":"dernst","access_level":"open_access","content_type":"application/pdf","checksum":"7de2dcb50deb65dde05c80082bb85a82","file_size":3057631,"success":1,"file_id":"18608","file_name":"2024_PloSBio_Kim.pdf","date_created":"2024-12-03T08:56:53Z","relation":"main_file"}],"OA_type":"gold","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publication_identifier":{"eissn":["1545-7885"],"issn":["1544-9173"]},"OA_place":"publisher","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","article_processing_charge":"Yes","article_number":"e3002879","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"oa":1,"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"publisher":"Public Library of Science","ec_funded":1,"APC_amount":"6248,82 EUR","date_updated":"2026-04-16T12:20:34Z","publication_status":"published","date_published":"2024-11-18T00:00:00Z","month":"11","article_type":"original"},{"title":"Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory","related_material":{"record":[{"relation":"dissertation_contains","id":"18681","status":"public"},{"relation":"later_version","id":"18879","status":"public"}]},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2024.05.02.592169","open_access":"1"}],"language":[{"iso":"eng"}],"department":[{"_id":"JoDa"},{"_id":"PeJo"}],"day":"02","abstract":[{"text":"The human brain has remarkable computational power. It generates sophisticated behavioral sequences, stores engrams over an individual’s lifetime, and produces higher cognitive functions up to the level of consciousness. However, so little of our neuroscience knowledge covers the human brain, and it remains unknown whether this organ is truly unique, or is a scaled version of the extensively studied rodent brain. To address this fundamental question, we determined the cellular, synaptic, and connectivity rules of the hippocampal CA3 recurrent circuit using multicellular patch clamp-recording. This circuit is the largest autoassociative network in the brain, and plays a key role in memory and higher-order computations such as pattern separation and pattern completion. We demonstrate that human hippocampal CA3 employs sparse connectivity, in stark contrast to neocortical recurrent networks. Connectivity sparsifies from rodents to humans, providing a circuit architecture that maximizes associational power. Unitary synaptic events at human CA3–CA3 synapses showed both distinct species-specific and circuit-dependent properties, with high reliability, unique amplitude precision, and long integration times. We also identify differential scaling rules between hippocampal pathways from rodents to humans, with a moderate increase in the convergence of CA3 inputs per cell, but a marked increase in human mossy fiber innervation. Anatomically guided full-scale modeling suggests that the human brain’s sparse connectivity, expanded neuronal number, and reliable synaptic signaling combine to enhance the associative memory storage capacity of CA3. Together, our results reveal unique rules of connectivity and synaptic signaling in the human hippocampus, demonstrating the absolute necessity of human brain research and beginning to unravel the remarkable performance of our autoassociative memory circuits.","lang":"eng"}],"article_processing_charge":"No","date_created":"2024-12-19T11:35:08Z","month":"05","date_published":"2024-05-02T00:00:00Z","publication_status":"draft","date_updated":"2026-04-14T08:34:32Z","ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"ScienComp"}],"author":[{"last_name":"Watson","first_name":"Jake F.","full_name":"Watson, Jake F."},{"full_name":"Vargas-Barroso, Victor","first_name":"Victor","last_name":"Vargas-Barroso"},{"last_name":"Morse-Mora","first_name":"Rebecca J.","full_name":"Morse-Mora, Rebecca J."},{"last_name":"Navas-Olive","full_name":"Navas-Olive, Andrea","first_name":"Andrea"},{"last_name":"Tavakoli","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","first_name":"Mojtaba"},{"first_name":"Johann G","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","last_name":"Danzl"},{"last_name":"Tomschik","first_name":"Matthias","full_name":"Tomschik, Matthias"},{"last_name":"Rössler","full_name":"Rössler, Karl","first_name":"Karl"},{"last_name":"Jonas","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M"}],"status":"public","year":"2024","corr_author":"1","project":[{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","call_identifier":"H2020"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"},{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","grant_number":"26137"}],"doi":"10.1101/2024.05.02.592169","_id":"18688","publication":"bioRxiv","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"preprint","OA_place":"repository","citation":{"chicago":"Watson, Jake F., Victor Vargas-Barroso, Rebecca J. Morse-Mora, Andrea Navas-Olive, Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.05.02.592169\">https://doi.org/10.1101/2024.05.02.592169</a>.","short":"J.F. Watson, V. Vargas-Barroso, R.J. Morse-Mora, A. Navas-Olive, M. Tavakoli, J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, BioRxiv (n.d.).","ista":"Watson JF, Vargas-Barroso V, Morse-Mora RJ, Navas-Olive A, Tavakoli M, Danzl JG, Tomschik M, Rössler K, Jonas PM. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. bioRxiv, <a href=\"https://doi.org/10.1101/2024.05.02.592169\">10.1101/2024.05.02.592169</a>.","apa":"Watson, J. F., Vargas-Barroso, V., Morse-Mora, R. J., Navas-Olive, A., Tavakoli, M., Danzl, J. G., … Jonas, P. M. (n.d.). Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.05.02.592169\">https://doi.org/10.1101/2024.05.02.592169</a>","ama":"Watson JF, Vargas-Barroso V, Morse-Mora RJ, et al. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.05.02.592169\">10.1101/2024.05.02.592169</a>","ieee":"J. F. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory,” <i>bioRxiv</i>. .","mla":"Watson, Jake F., et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.05.02.592169\">10.1101/2024.05.02.592169</a>."},"acknowledgement":"We thank Florian Marr for excellent technical assistance, Christina Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor Asenov for development of the transportation box for human brain tissue, Tim Vogels for guidance on simulations, Marcus Huber for mathematical advice, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA, and we are particularly grateful for assistance from Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Life Science Facility, Miba Machine Shop, and Scientific Computing. We also acknowledge the excellent support of the Medical University of Vienna Department of Neurosurgery staff, Romana Hoeftberger and the Division of Neuropathology and Neurochemistry, and Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund (FWF; grant PAT 4178023 to P.J.; grant DK W1232 to M.R.T. and J.G.D.) and the Austrian Academy of Sciences (DOC fellowship 26137 to M.R.T.).","oa_version":"Preprint"},{"page":"755-771.e9","author":[{"last_name":"Chen","first_name":"JingJing","full_name":"Chen, JingJing","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kaufmann","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","full_name":"Kaufmann, Walter"},{"first_name":"Chong","full_name":"Chen, Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","last_name":"Chen"},{"last_name":"Arai","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","full_name":"Arai, Itaru","first_name":"Itaru"},{"full_name":"Kim, Olena","first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2344-1039","last_name":"Kim"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"quality_controlled":"1","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","grant_number":"25383","_id":"26B66A3E-B435-11E9-9278-68D0E5697425"}],"_id":"14843","doi":"10.1016/j.neuron.2023.12.002","publication":"Neuron","type":"journal_article","intvolume":"       112","ddc":["570"],"external_id":{"isi":["001202925700001"],"pmid":["38215739"]},"citation":{"chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>.","short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron 112 (2024) 755–771.e9.","ista":"Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. 2024. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 112(5), 755–771.e9.","apa":"Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38; Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>","ama":"Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. 2024;112(5):755-771.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>","mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, vol. 112, no. 5, Elsevier, 2024, p. 755–771.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>.","ieee":"J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” <i>Neuron</i>, vol. 112, no. 5. Elsevier, p. 755–771.e9, 2024."},"acknowledgement":"We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C.","volume":112,"file_date_updated":"2025-04-23T14:02:08Z","related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/","description":"News on ISTA Website"}],"record":[{"id":"15101","relation":"dissertation_contains","status":"public"}]},"language":[{"iso":"eng"}],"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","date_created":"2024-01-21T23:00:56Z","day":"06","abstract":[{"text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.","lang":"eng"}],"isi":1,"scopus_import":"1","pmid":1,"status":"public","issue":"5","year":"2024","has_accepted_license":"1","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["0896-6273"],"eissn":["1097-4199"]},"OA_place":"publisher","OA_type":"hybrid","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"oa_version":"Published Version","file":[{"file_id":"19614","relation":"main_file","file_name":"2024_Neuron_Chen.pdf","date_created":"2025-04-23T14:02:08Z","date_updated":"2025-04-23T14:02:08Z","success":1,"creator":"dernst","file_size":8192355,"checksum":"30098b4f0209556ddfb3540a23d07ca5","access_level":"open_access","content_type":"application/pdf"}],"oa":1,"department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"article_processing_charge":"Yes (via OA deal)","PlanS_conform":"1","date_updated":"2026-06-29T22:30:22Z","publication_status":"published","article_type":"original","month":"03","date_published":"2024-03-06T00:00:00Z","ec_funded":1,"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"publisher":"Elsevier"},{"_id":"15084","doi":"10.1073/pnas.2301449121","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020","grant_number":"694539"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","call_identifier":"H2020","name":"International IST Doctoral Program"}],"quality_controlled":"1","author":[{"orcid":"0000-0002-3509-1948","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter","first_name":"Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bhandari, Pradeep","first_name":"Pradeep","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481","last_name":"Bhandari"},{"first_name":"Hüseyin C","full_name":"Önal, Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2771-2011","last_name":"Önal"},{"orcid":"0000-0003-0005-401X","last_name":"Borges Merjane","first_name":"Carolina","full_name":"Borges Merjane, Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Le Monnier, Elodie","first_name":"Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","last_name":"Le Monnier"},{"id":"4d26cf11-5355-11ee-ae5a-eb05e255b9b2","full_name":"Roy, Utsa","first_name":"Utsa","last_name":"Roy"},{"last_name":"Nakamura","full_name":"Nakamura, Yukihiro","first_name":"Yukihiro"},{"first_name":"Tetsushi","full_name":"Sadakata, Tetsushi","last_name":"Sadakata"},{"first_name":"Makoto","full_name":"Sanbo, Makoto","last_name":"Sanbo"},{"full_name":"Hirabayashi, Masumi","first_name":"Masumi","last_name":"Hirabayashi"},{"full_name":"Rhee, JeongSeop","first_name":"JeongSeop","last_name":"Rhee"},{"last_name":"Brose","first_name":"Nils","full_name":"Brose, Nils"},{"last_name":"Jonas","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M"},{"orcid":"0000-0001-8761-9444","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"}],"ddc":["570"],"external_id":{"isi":["001208567300006"],"pmid":["38346189"]},"acknowledgement":"We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support.","citation":{"ieee":"P. Koppensteiner <i>et al.</i>, “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 8. National Academy of Sciences, 2024.","mla":"Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>.","apa":"Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>","ama":"Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(8). doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>","ista":"Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. 121(8), e2301449121.","chicago":"Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>.","short":"P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the United States of America 121 (2024)."},"intvolume":"       121","type":"journal_article","publication":"Proceedings of the National Academy of Sciences of the United States of America","date_created":"2024-03-05T09:23:55Z","day":"20","abstract":[{"lang":"eng","text":"GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n            <jats:sup>2+</jats:sup>\r\n            -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals."}],"language":[{"iso":"eng"}],"related_material":{"record":[{"status":"public","id":"13173","relation":"research_data"},{"status":"public","id":"19271","relation":"dissertation_contains"}],"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/","description":"News on ISTA Website"}]},"title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","volume":121,"file_date_updated":"2024-03-12T13:42:42Z","pmid":1,"scopus_import":"1","isi":1,"corr_author":"1","has_accepted_license":"1","status":"public","year":"2024","issue":"8","oa_version":"Published Version","file":[{"success":1,"creator":"dernst","checksum":"b25b2a057c266ff317a48b0d54d6fc8a","access_level":"open_access","file_size":13648221,"content_type":"application/pdf","date_updated":"2024-03-12T13:42:42Z","relation":"main_file","file_name":"2024_PNAS_Koppensteiner.pdf","date_created":"2024-03-12T13:42:42Z","file_id":"15110"}],"OA_type":"hybrid","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"OA_place":"publisher","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","article_processing_charge":"Yes (in subscription journal)","article_number":"e2301449121","department":[{"_id":"RySh"},{"_id":"PeJo"}],"oa":1,"publisher":"National Academy of Sciences","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"ec_funded":1,"date_updated":"2026-06-29T22:30:27Z","publication_status":"published","APC_amount":"5887,8 EUR","article_type":"original","date_published":"2024-02-20T00:00:00Z","month":"02"},{"file_date_updated":"2023-03-27T06:51:09Z","volume":18,"title":"Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy","language":[{"iso":"eng"}],"day":"17","abstract":[{"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.","lang":"eng"}],"date_created":"2023-03-26T22:01:07Z","isi":1,"scopus_import":"1","pmid":1,"author":[{"first_name":"Jason Seth","full_name":"Rothman, Jason Seth","last_name":"Rothman"},{"last_name":"Borges Merjane","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina","full_name":"Borges Merjane, Carolina"},{"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","orcid":"0000-0001-5001-4804","last_name":"Jonas"},{"last_name":"Angus Silver","first_name":"R.","full_name":"Angus Silver, R."}],"quality_controlled":"1","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"V00739","name":"Structural plasticity at mossy fiber-CA3 synapses"}],"doi":"10.1371/journal.pone.0277148","_id":"12759","publication":"PLoS ONE","type":"journal_article","intvolume":"        18","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).","citation":{"mla":"Rothman, Jason Seth, et al. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” <i>PLoS ONE</i>, vol. 18, no. 3 March, e0277148, Public Library of Science, 2023, doi:<a href=\"https://doi.org/10.1371/journal.pone.0277148\">10.1371/journal.pone.0277148</a>.","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,” <i>PLoS ONE</i>, vol. 18, no. 3 March. Public Library of Science, 2023.","apa":"Rothman, J. S., Borges Merjane, C., Holderith, N., Jonas, P. M., &#38; Angus Silver, R. (2023). Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. <i>PLoS ONE</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0277148\">https://doi.org/10.1371/journal.pone.0277148</a>","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. <i>PLoS ONE</i>. 2023;18(3 March). doi:<a href=\"https://doi.org/10.1371/journal.pone.0277148\">10.1371/journal.pone.0277148</a>","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.","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.” <i>PLoS ONE</i>. Public Library of Science, 2023. <a href=\"https://doi.org/10.1371/journal.pone.0277148\">https://doi.org/10.1371/journal.pone.0277148</a>.","short":"J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver, PLoS ONE 18 (2023)."},"external_id":{"isi":["001024737400001"],"pmid":["36930689"]},"ddc":["570"],"oa":1,"department":[{"_id":"PeJo"}],"article_number":"e0277148","article_processing_charge":"No","article_type":"original","date_published":"2023-03-17T00:00:00Z","month":"03","publication_status":"published","date_updated":"2025-04-23T08:50:50Z","ec_funded":1,"acknowledged_ssus":[{"_id":"EM-Fac"}],"publisher":"Public Library of Science","issue":"3 March","year":"2023","status":"public","has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["1932-6203"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"file":[{"date_updated":"2023-03-27T06:51:09Z","success":1,"content_type":"application/pdf","file_size":7290413,"access_level":"open_access","checksum":"2380331ec27cc87808826fc64419ac1c","creator":"dernst","file_id":"12770","relation":"main_file","date_created":"2023-03-27T06:51:09Z","file_name":"2023_PLoSOne_Rothman.pdf"}],"oa_version":"Published Version"},{"oa_version":"Published Version","file":[{"creator":"dernst","access_level":"open_access","content_type":"application/pdf","checksum":"a68e845780a82ea36d0d4d3212a87c10","file_size":14103039,"success":1,"date_updated":"2025-02-26T08:01:57Z","file_name":"2023_NatureMethods_Velicky.pdf","date_created":"2025-02-26T08:01:57Z","relation":"main_file","file_id":"19088"}],"OA_type":"hybrid","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"OA_place":"publisher","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","corr_author":"1","status":"public","year":"2023","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"publisher":"Springer Nature","ec_funded":1,"publication_status":"published","date_updated":"2026-04-07T12:58:30Z","date_published":"2023-08-01T00:00:00Z","month":"08","article_type":"original","article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"oa":1,"ddc":["570"],"external_id":{"isi":["001025621500001"],"pmid":["37429995"]},"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.).","citation":{"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.","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.","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.” <i>Nature Methods</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>.","ieee":"P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>","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. <i>Nature Methods</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>"},"intvolume":"        20","type":"journal_article","publication":"Nature Methods","_id":"13267","doi":"10.1038/s41592-023-01936-6","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"call_identifier":"FWF","grant_number":"W1232","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"grant_number":"LS18-022","name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"name":"International IST Doctoral Program","grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"24F9549A-B435-11E9-9278-68D0E5697425","grant_number":"715767","call_identifier":"H2020","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","grant_number":"715508"},{"call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","grant_number":"101026635"},{"_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration"}],"quality_controlled":"1","author":[{"last_name":"Velicky","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","first_name":"Philipp"},{"first_name":"Eder","full_name":"Miguel Villalba, Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5665-0430","last_name":"Miguel Villalba"},{"orcid":"0000-0003-3862-1235","last_name":"Michalska","full_name":"Michalska, Julia M","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik"},{"full_name":"Wei, Donglai","first_name":"Donglai","last_name":"Wei"},{"first_name":"Zudi","full_name":"Lin, Zudi","last_name":"Lin"},{"orcid":"0000-0002-8698-3823","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"full_name":"Troidl, Jakob","first_name":"Jakob","last_name":"Troidl"},{"full_name":"Beyer, Johanna","first_name":"Johanna","last_name":"Beyer"},{"first_name":"Yoav","full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon"},{"orcid":"0000-0003-1216-9105","last_name":"Sommer","full_name":"Sommer, Christoph M","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke","first_name":"Wiebke","last_name":"Jahr","orcid":"0000-0003-0201-2315"},{"last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","full_name":"Cenameri, Alban"},{"first_name":"Johannes","full_name":"Broichhagen, Johannes","last_name":"Broichhagen"},{"first_name":"Seth G.N.","full_name":"Grant, Seth G.N.","last_name":"Grant"},{"full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"},{"first_name":"Gaia","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"first_name":"Hanspeter","full_name":"Pfister, Hanspeter","last_name":"Pfister"},{"orcid":"0000-0001-6511-9385","last_name":"Bickel","full_name":"Bickel, Bernd","first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973"}],"page":"1256-1265","pmid":1,"scopus_import":"1","isi":1,"date_created":"2023-07-23T22:01:13Z","day":"01","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."}],"language":[{"iso":"eng"}],"related_material":{"record":[{"status":"public","relation":"research_data","id":"12817"},{"status":"public","id":"14770","relation":"shorter_version"},{"status":"public","relation":"earlier_version","id":"11943"},{"status":"public","relation":"dissertation_contains","id":"18674"}],"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}]},"title":"Dense 4D nanoscale reconstruction of living brain tissue","volume":20,"file_date_updated":"2025-02-26T08:01:57Z"},{"pmid":1,"isi":1,"scopus_import":"1","date_created":"2022-08-24T08:25:50Z","day":"16","abstract":[{"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.","lang":"eng"}],"volume":13,"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"file_date_updated":"2022-08-26T11:51:40Z","language":[{"iso":"eng"}],"title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","intvolume":"        13","ddc":["570"],"external_id":{"pmid":["35974109"],"isi":["000841396400008"]},"citation":{"mla":"Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” <i>Nature Communications</i>, vol. 13, 4826, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32559-8\">10.1038/s41467-022-32559-8</a>.","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,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","apa":"Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., &#38; Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32559-8\">https://doi.org/10.1038/s41467-022-32559-8</a>","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. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32559-8\">10.1038/s41467-022-32559-8</a>","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.","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.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32559-8\">https://doi.org/10.1038/s41467-022-32559-8</a>.","short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022)."},"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.).","publication":"Nature Communications","type":"journal_article","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"grant_number":"Z00312","call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"_id":"11951","doi":"10.1038/s41467-022-32559-8","author":[{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"},{"id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","first_name":"Karola","full_name":"Käfer, Karola","last_name":"Käfer"},{"last_name":"Velicky","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","first_name":"Philipp"},{"full_name":"Csicsvari, Jozsef L","first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5193-4036","last_name":"Csicsvari"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973"},{"last_name":"Jonas","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M"}],"quality_controlled":"1","ec_funded":1,"publisher":"Springer Nature","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"publication_status":"published","date_updated":"2025-06-12T06:10:44Z","article_type":"original","date_published":"2022-08-16T00:00:00Z","month":"08","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"article_number":"4826","article_processing_charge":"No","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"oa_version":"Published Version","file":[{"date_updated":"2022-08-26T11:51:40Z","creator":"dernst","access_level":"open_access","content_type":"application/pdf","file_size":5910357,"checksum":"405936d9e4d33625d80c093c9713a91f","success":1,"file_id":"11990","file_name":"2022_NatureCommunications_BenSimon.pdf","date_created":"2022-08-26T11:51:40Z","relation":"main_file"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["2041-1723"]},"has_accepted_license":"1","corr_author":"1","year":"2022","status":"public"},{"ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"publisher":"eLife Sciences Publications","date_published":"2022-09-15T00:00:00Z","article_type":"original","month":"09","publication_status":"published","date_updated":"2025-04-15T08:29:05Z","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"article_number":"79848","article_processing_charge":"No","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"file":[{"date_updated":"2023-01-30T11:50:53Z","creator":"dernst","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","file_size":8506811,"access_level":"open_access","content_type":"application/pdf","success":1,"file_id":"12463","file_name":"2022_eLife_Sumser.pdf","date_created":"2023-01-30T11:50:53Z","relation":"main_file"}],"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_identifier":{"eissn":["2050-084X"]},"corr_author":"1","has_accepted_license":"1","status":"public","year":"2022","pmid":1,"isi":1,"scopus_import":"1","abstract":[{"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.","lang":"eng"}],"day":"15","date_created":"2023-01-16T10:04:15Z","file_date_updated":"2023-01-30T11:50:53Z","volume":11,"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","language":[{"iso":"eng"}],"intvolume":"        11","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).","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. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>","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,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","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.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>.","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."},"ddc":["570"],"external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"publication":"eLife","type":"journal_article","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"_id":"2634E9D2-B435-11E9-9278-68D0E5697425","name":"Circuits of Visual Attention","grant_number":"756502","call_identifier":"H2020"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","grant_number":"Z00312"},{"grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"name":"Connecting sensory with motor processing in the superior colliculus","grant_number":"ALTF 1098-2017","_id":"264FEA02-B435-11E9-9278-68D0E5697425"}],"doi":"10.7554/elife.79848","_id":"12288","author":[{"id":"3320A096-F248-11E8-B48F-1D18A9856A87","full_name":"Sumser, Anton L","first_name":"Anton L","last_name":"Sumser","orcid":"0000-0002-4792-1881"},{"last_name":"Jösch","orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","full_name":"Jösch, Maximilian A","first_name":"Maximilian A"},{"first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"},{"first_name":"Yoav","full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon"}],"quality_controlled":"1"},{"status":"public","author":[{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","full_name":"Velicky, Philipp","last_name":"Velicky","orcid":"0000-0002-2340-7431"},{"last_name":"Miguel Villalba","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder","full_name":"Miguel Villalba, Eder"},{"orcid":"0000-0003-3862-1235","last_name":"Michalska","full_name":"Michalska, Julia M","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Wei","full_name":"Wei, Donglai","first_name":"Donglai"},{"first_name":"Zudi","full_name":"Lin, Zudi","last_name":"Lin"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","first_name":"Jake","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"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","full_name":"Ben Simon, Yoav","last_name":"Ben Simon"},{"orcid":"0000-0003-1216-9105","last_name":"Sommer","full_name":"Sommer, Christoph M","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jahr","orcid":"0000-0003-0201-2315","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke","first_name":"Wiebke"},{"last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","full_name":"Cenameri, Alban"},{"last_name":"Broichhagen","full_name":"Broichhagen, Johannes","first_name":"Johannes"},{"last_name":"Grant","full_name":"Grant, Seth G. N.","first_name":"Seth G. N."},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Pfister, Hanspeter","first_name":"Hanspeter","last_name":"Pfister"},{"first_name":"Bernd","full_name":"Bickel, Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385","last_name":"Bickel"},{"full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","last_name":"Danzl"}],"year":"2022","corr_author":"1","doi":"10.1101/2022.03.16.484431","_id":"11943","publication":"bioRxiv","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"preprint","OA_place":"repository","citation":{"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, <a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>.","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.).","ieee":"P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","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. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>"},"oa_version":"Preprint","title":"Saturated reconstruction of living brain tissue","main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"related_material":{"record":[{"id":"13267","relation":"later_version","status":"public"},{"id":"12470","relation":"dissertation_contains","status":"public"}]},"language":[{"iso":"eng"}],"oa":1,"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"day":"09","article_processing_charge":"No","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 <jats:italic>in-silico</jats:italic> reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches<jats:sup>6–12</jats:sup> 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) microscopy<jats:sup>6,13</jats:sup> in extracellularly labelled tissue<jats:sup>14</jats:sup> 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."}],"date_created":"2022-08-23T11:07:59Z","date_published":"2022-05-09T00:00:00Z","month":"05","publication_status":"draft","date_updated":"2026-06-29T22:30:09Z","publisher":"Cold Spring Harbor Laboratory"},{"publication":"bioRxiv","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"preprint","oa_version":"Preprint","citation":{"ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","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. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>","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, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","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.)."},"year":"2022","status":"public","author":[{"orcid":"0000-0003-3862-1235","last_name":"Michalska","first_name":"Julia M","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik"},{"last_name":"Velicky","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","first_name":"Philipp"},{"last_name":"Korinkova","first_name":"Hana","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"orcid":"0000-0002-8698-3823","last_name":"Watson","full_name":"Watson, Jake","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"full_name":"Cenameri, Alban","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri"},{"last_name":"Sommer","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","first_name":"Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403"},{"last_name":"Roessler","first_name":"Karl","full_name":"Roessler, Karl"},{"full_name":"Czech, Thomas","first_name":"Thomas","last_name":"Czech"},{"first_name":"Sandra","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","last_name":"Siegert"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178"},{"first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"},{"orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"_id":"11950","doi":"10.1101/2022.08.17.504272","corr_author":"1","date_updated":"2026-06-29T22:30:09Z","publication_status":"draft","date_published":"2022-08-18T00:00:00Z","month":"08","publisher":"Cold Spring Harbor Laboratory","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12470"}]},"oa":1,"language":[{"iso":"eng"}],"main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","date_created":"2022-08-24T08:24:52Z","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."}],"day":"18","article_processing_charge":"No","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}]},{"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. <i>Journal of Neuroscience Methods</i>. 2021;357(6). doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">10.1016/j.jneumeth.2021.109125</a>","apa":"Zhang, X., Schlögl, A., Vandael, D. H., &#38; Jonas, P. M. (2021). MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. <i>Journal of Neuroscience Methods</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">https://doi.org/10.1016/j.jneumeth.2021.109125</a>","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,” <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6. Elsevier, 2021.","mla":"Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6, 109125, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">10.1016/j.jneumeth.2021.109125</a>.","short":"X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021).","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.” <i>Journal of Neuroscience Methods</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">https://doi.org/10.1016/j.jneumeth.2021.109125</a>.","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."},"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.","external_id":{"pmid":["33711356"],"isi":["000661088500005"]},"ddc":["570"],"intvolume":"       357","publication":"Journal of Neuroscience Methods","type":"journal_article","doi":"10.1016/j.jneumeth.2021.109125","_id":"9329","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","call_identifier":"FWF"}],"quality_controlled":"1","author":[{"last_name":"Zhang","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","full_name":"Zhang, Xiaomin"},{"orcid":"0000-0002-5621-8100","last_name":"Schlögl","full_name":"Schlögl, Alois","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Vandael","orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","full_name":"Vandael, David H"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"pmid":1,"scopus_import":"1","isi":1,"abstract":[{"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.","lang":"eng"}],"day":"09","date_created":"2021-04-18T22:01:39Z","title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","language":[{"iso":"eng"}],"file_date_updated":"2021-04-19T08:30:22Z","volume":357,"file":[{"file_id":"9339","relation":"main_file","date_created":"2021-04-19T08:30:22Z","file_name":"2021_JourNeuroscienceMeth_Zhang.pdf","date_updated":"2021-04-19T08:30:22Z","success":1,"file_size":6924738,"checksum":"2a5800d91b96d08b525e17319dcd5e44","access_level":"open_access","content_type":"application/pdf","creator":"dernst"}],"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"publication_identifier":{"issn":["0165-0270"],"eissn":["1872-678X"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","year":"2021","status":"public","issue":"6","acknowledged_ssus":[{"_id":"SSU"}],"publisher":"Elsevier","ec_funded":1,"date_published":"2021-03-09T00:00:00Z","article_type":"original","month":"03","date_updated":"2025-06-12T06:39:15Z","publication_status":"published","article_processing_charge":"Yes (via OA deal)","article_number":"109125","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"oa":1},{"scopus_import":"1","isi":1,"pmid":1,"title":"Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses","related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/"}]},"language":[{"iso":"eng"}],"file_date_updated":"2021-12-17T11:34:50Z","keyword":["general physics and astronomy","general biochemistry","genetics and molecular biology","general chemistry"],"volume":12,"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."}],"day":"18","date_created":"2021-08-06T07:22:55Z","type":"journal_article","publication":"Nature Communications","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.","citation":{"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.","chicago":"Vandael, David H, Yuji Okamoto, and Peter M Jonas. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” <i>Nature Communications</i>. Springer, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23153-5\">https://doi.org/10.1038/s41467-021-23153-5</a>.","short":"D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021).","ieee":"D. H. Vandael, Y. Okamoto, and P. M. Jonas, “Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses,” <i>Nature Communications</i>, vol. 12, no. 1. Springer, 2021.","mla":"Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” <i>Nature Communications</i>, vol. 12, no. 1, 2912, Springer, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23153-5\">10.1038/s41467-021-23153-5</a>.","apa":"Vandael, D. H., Okamoto, Y., &#38; Jonas, P. M. (2021). Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. <i>Nature Communications</i>. Springer. <a href=\"https://doi.org/10.1038/s41467-021-23153-5\">https://doi.org/10.1038/s41467-021-23153-5</a>","ama":"Vandael DH, Okamoto Y, Jonas PM. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23153-5\">10.1038/s41467-021-23153-5</a>"},"external_id":{"pmid":["34006874"],"isi":["000655481800014"]},"ddc":["570"],"intvolume":"        12","quality_controlled":"1","author":[{"last_name":"Vandael","orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","full_name":"Vandael, David H"},{"id":"3337E116-F248-11E8-B48F-1D18A9856A87","first_name":"Yuji","full_name":"Okamoto, Yuji","last_name":"Okamoto","orcid":"0000-0003-0408-6094"},{"full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"doi":"10.1038/s41467-021-23153-5","_id":"9778","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","grant_number":"Z00312"}],"article_type":"original","month":"05","date_published":"2021-05-18T00:00:00Z","publication_status":"published","date_updated":"2025-06-12T06:28:45Z","publisher":"Springer","acknowledged_ssus":[{"_id":"SSU"}],"ec_funded":1,"oa":1,"article_processing_charge":"Yes","department":[{"_id":"PeJo"}],"article_number":"2912","OA_place":"publisher","publication_identifier":{"issn":["2041-1723"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"date_updated":"2021-12-17T11:34:50Z","success":1,"checksum":"6036a8cdae95e1707c2a04d54e325ff4","access_level":"open_access","content_type":"application/pdf","file_size":3108845,"creator":"kschuh","file_id":"10563","relation":"main_file","date_created":"2021-12-17T11:34:50Z","file_name":"2021_NatureCommunications_Vandael.pdf"}],"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"OA_type":"gold","status":"public","issue":"1","year":"2021","has_accepted_license":"1","corr_author":"1"},{"_id":"10816","doi":"10.1038/s43588-021-00157-1","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","grant_number":"Z00312"}],"quality_controlled":"1","page":"830-842","author":[{"last_name":"Guzmán","orcid":"0000-0003-2209-5242","id":"30CC5506-F248-11E8-B48F-1D18A9856A87","first_name":"José","full_name":"Guzmán, José"},{"orcid":"0000-0002-5621-8100","last_name":"Schlögl","first_name":"Alois","full_name":"Schlögl, Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87"},{"id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia ","full_name":"Espinoza Martinez, Claudia ","last_name":"Espinoza Martinez","orcid":"0000-0003-4710-2082"},{"id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","full_name":"Zhang, Xiaomin","last_name":"Zhang","orcid":"0000-0003-0256-6529"},{"full_name":"Suter, Benjamin","first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9885-6936","last_name":"Suter"},{"first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"external_id":{"isi":["000888567500015"]},"ddc":["610"],"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. <i>Nature Computational Science</i>. 2021;1(12):830-842. doi:<a href=\"https://doi.org/10.1038/s43588-021-00157-1\">10.1038/s43588-021-00157-1</a>","apa":"Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &#38; Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. <i>Nature Computational Science</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s43588-021-00157-1\">https://doi.org/10.1038/s43588-021-00157-1</a>","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,” <i>Nature Computational Science</i>, vol. 1, no. 12. Springer Nature, pp. 830–842, 2021.","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.” <i>Nature Computational Science</i>, vol. 1, no. 12, Springer Nature, 2021, pp. 830–42, doi:<a href=\"https://doi.org/10.1038/s43588-021-00157-1\">10.1038/s43588-021-00157-1</a>.","short":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, Nature Computational Science 1 (2021) 830–842.","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.” <i>Nature Computational Science</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s43588-021-00157-1\">https://doi.org/10.1038/s43588-021-00157-1</a>.","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."},"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.).","intvolume":"         1","type":"journal_article","publication":"Nature Computational Science","date_created":"2022-03-04T08:32:36Z","abstract":[{"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.","lang":"eng"}],"day":"16","main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/647800"}],"related_material":{"record":[{"status":"public","id":"10110","relation":"software"}],"link":[{"url":"https://ista.ac.at/en/news/spot-the-difference/","relation":"press_release"}]},"language":[{"iso":"eng"}],"title":"How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network","volume":1,"keyword":["general medicine"],"file_date_updated":"2022-06-18T22:30:03Z","scopus_import":"1","isi":1,"has_accepted_license":"1","corr_author":"1","status":"public","issue":"12","year":"2021","oa_version":"Submitted Version","file":[{"date_updated":"2022-06-18T22:30:03Z","content_type":"application/pdf","file_size":1699466,"access_level":"open_access","checksum":"9fec5b667909ef52be96d502e4f8c2ae","creator":"patrickd","file_id":"11430","relation":"main_file","embargo":"2022-06-17","date_created":"2022-06-02T12:51:07Z","file_name":"Guzmanetal2021.pdf"},{"title":"Supplementary Material","file_id":"11431","file_name":"Guzmanetal2021Suppl.pdf","embargo":"2022-06-17","date_created":"2022-06-02T12:53:47Z","relation":"supplementary_material","date_updated":"2022-06-18T22:30:03Z","creator":"patrickd","file_size":3005651,"checksum":"52a005b13a114e3c3a28fa6bbe8b1a8d","content_type":"application/pdf","access_level":"open_access"}],"publication_identifier":{"issn":["2662-8457"]},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","article_processing_charge":"No","department":[{"_id":"PeJo"}],"oa":1,"acknowledged_ssus":[{"_id":"SSU"}],"publisher":"Springer Nature","ec_funded":1,"date_updated":"2025-10-09T22:30:54Z","publication_status":"published","date_published":"2021-12-16T00:00:00Z","month":"12","article_type":"original"},{"has_accepted_license":"1","_id":"10110","doi":"10.15479/AT:ISTA:10110","status":"public","author":[{"orcid":"0000-0003-2209-5242","last_name":"Guzmán","first_name":"José","full_name":"Guzmán, José","id":"30CC5506-F248-11E8-B48F-1D18A9856A87"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois","full_name":"Schlögl, Alois","last_name":"Schlögl","orcid":"0000-0002-5621-8100"},{"last_name":"Espinoza Martinez","orcid":"0000-0003-4710-2082","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia ","full_name":"Espinoza Martinez, Claudia "},{"orcid":"0000-0003-0256-6529","last_name":"Zhang","full_name":"Zhang, Xiaomin","first_name":"Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Suter, Benjamin","first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9885-6936","last_name":"Suter"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"year":"2021","tmp":{"name":"GNU General Public License 3.0","legal_code_url":"https://www.gnu.org/licenses/gpl-3.0.en.html","short":"GPL 3.0"},"ddc":["005"],"citation":{"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, <a href=\"https://doi.org/10.15479/AT:ISTA:10110\">10.15479/AT:ISTA:10110</a>.","short":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, (2021).","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. <a href=\"https://doi.org/10.15479/AT:ISTA:10110\">https://doi.org/10.15479/AT:ISTA:10110</a>.","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.","mla":"Guzmán, José, et al. <i>How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network</i>. IST Austria, 2021, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10110\">10.15479/AT:ISTA:10110</a>.","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:<a href=\"https://doi.org/10.15479/AT:ISTA:10110\">10.15479/AT:ISTA:10110</a>","apa":"Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &#38; 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. <a href=\"https://doi.org/10.15479/AT:ISTA:10110\">https://doi.org/10.15479/AT:ISTA:10110</a>"},"file":[{"success":1,"creator":"cchlebak","checksum":"f92f8931cad0aa7e411c1715337bf408","access_level":"open_access","file_size":332990101,"content_type":"application/x-zip-compressed","date_updated":"2021-10-08T08:46:04Z","relation":"main_file","file_name":"patternseparation-main (1).zip","date_created":"2021-10-08T08:46:04Z","file_id":"10114"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","type":"software","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"date_created":"2021-10-08T06:44:22Z","day":"16","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."}],"file_date_updated":"2021-10-08T08:46:04Z","oa":1,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/spot-the-difference/","description":"News on IST Webpage","relation":"press_release"}],"record":[{"id":"10816","relation":"used_for_analysis_in","status":"public"}]},"license":"https://opensource.org/licenses/GPL-3.0","title":"How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network","publisher":"IST Austria","date_updated":"2026-06-29T22:30:49Z","date_published":"2021-12-16T00:00:00Z","month":"12"},{"article_processing_charge":"No","department":[{"_id":"PeJo"}],"oa":1,"publisher":"Springer Nature","acknowledged_ssus":[{"_id":"M-Shop"}],"ec_funded":1,"article_type":"original","month":"06","date_published":"2021-06-01T00:00:00Z","date_updated":"2025-04-22T22:30:43Z","publication_status":"published","has_accepted_license":"1","corr_author":"1","status":"public","year":"2021","issue":"6","file":[{"date_updated":"2021-12-02T23:30:05Z","creator":"cziletti","access_level":"open_access","content_type":"application/pdf","file_size":38574802,"checksum":"7eb580abd8893cdb0b410cf41bc8c263","file_id":"9639","relation":"main_file","file_name":"VandaeletalAuthorVersion2021.pdf","date_created":"2021-07-08T12:27:55Z","embargo":"2021-12-01"}],"oa_version":"Submitted Version","publication_identifier":{"issn":["1754-2189"],"eissn":["1750-2799"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"01","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."}],"date_created":"2021-05-30T22:01:24Z","title":"Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses","language":[{"iso":"eng"}],"file_date_updated":"2021-12-02T23:30:05Z","volume":16,"pmid":1,"scopus_import":"1","isi":1,"doi":"10.1038/s41596-021-00526-0","_id":"9438","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"V00739","name":"Structural plasticity at mossy fiber-CA3 synapses"}],"quality_controlled":"1","page":"2947–2967","author":[{"full_name":"Vandael, David H","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","last_name":"Vandael"},{"id":"3337E116-F248-11E8-B48F-1D18A9856A87","full_name":"Okamoto, Yuji","first_name":"Yuji","last_name":"Okamoto","orcid":"0000-0003-0408-6094"},{"id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane","orcid":"0000-0003-0005-401X"},{"id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M","full_name":"Vargas Barroso, Victor M","last_name":"Vargas Barroso"},{"id":"4952F31E-F248-11E8-B48F-1D18A9856A87","full_name":"Suter, Benjamin","first_name":"Benjamin","last_name":"Suter","orcid":"0000-0002-9885-6936"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804"}],"citation":{"short":"D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.","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.” <i>Nature Protocols</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>.","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.","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. <i>Nature Protocols</i>. 2021;16(6):2947–2967. doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>","apa":"Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter, B., &#38; Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. <i>Nature Protocols</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>","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,” <i>Nature Protocols</i>, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.","mla":"Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” <i>Nature Protocols</i>, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967, doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>."},"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.","external_id":{"isi":["000650528700003"],"pmid":["33990799"]},"ddc":["570"],"intvolume":"        16","publication":"Nature Protocols","type":"journal_article"},{"project":[{"grant_number":"694539","call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385"}],"_id":"9437","doi":"10.7554/ELIFE.68274","author":[{"orcid":"0000-0003-0863-4481","last_name":"Bhandari","full_name":"Bhandari, Pradeep","first_name":"Pradeep","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87"},{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","full_name":"Vandael, David H","last_name":"Vandael","orcid":"0000-0001-7577-1676"},{"full_name":"Fernández-Fernández, Diego","first_name":"Diego","last_name":"Fernández-Fernández"},{"last_name":"Fritzius","first_name":"Thorsten","full_name":"Fritzius, Thorsten"},{"last_name":"Kleindienst","first_name":"David","full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"id":"4659D740-F248-11E8-B48F-1D18A9856A87","full_name":"Önal, Hüseyin C","first_name":"Hüseyin C","last_name":"Önal","orcid":"0000-0002-2771-2011"},{"last_name":"Montanaro-Punzengruber","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","first_name":"Jacqueline-Claire"},{"last_name":"Gassmann","first_name":"Martin","full_name":"Gassmann, Martin"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804"},{"first_name":"Akos","full_name":"Kulik, Akos","last_name":"Kulik"},{"full_name":"Bettler, Bernhard","first_name":"Bernhard","last_name":"Bettler"},{"first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","last_name":"Shigemoto"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","first_name":"Peter","last_name":"Koppensteiner","orcid":"0000-0002-3509-1948"}],"quality_controlled":"1","intvolume":"        10","ddc":["570"],"external_id":{"pmid":["33913808"],"isi":["000651761700001"]},"citation":{"chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Cihan Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>.","short":"P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).","ista":"Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal C, 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.","apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>","ieee":"P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>."},"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.","publication":"eLife","type":"journal_article","date_created":"2021-05-30T22:01:23Z","abstract":[{"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.","lang":"eng"}],"day":"29","volume":10,"file_date_updated":"2021-05-31T09:43:09Z","related_material":{"link":[{"url":"https://doi.org/10.1101/2020.04.16.045112","relation":"earlier_version"}],"record":[{"status":"public","relation":"dissertation_contains","id":"19271"},{"status":"public","id":"9562","relation":"dissertation_contains"}]},"language":[{"iso":"eng"}],"title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","pmid":1,"isi":1,"scopus_import":"1","has_accepted_license":"1","year":"2021","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"oa_version":"Published Version","file":[{"success":1,"creator":"cziletti","access_level":"open_access","content_type":"application/pdf","file_size":8174719,"checksum":"6ebcb79999f889766f7cd79ee134ad28","date_updated":"2021-05-31T09:43:09Z","relation":"main_file","file_name":"2021_eLife_Bhandari.pdf","date_created":"2021-05-31T09:43:09Z","file_id":"9440"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["2050-084X"]},"department":[{"_id":"RySh"},{"_id":"PeJo"}],"article_number":"e68274","article_processing_charge":"No","oa":1,"ec_funded":1,"publisher":"eLife Sciences Publications","date_updated":"2026-06-29T22:31:05Z","publication_status":"published","date_published":"2021-04-29T00:00:00Z","month":"04","article_type":"original"}]