[{"isi":1,"publication":"Science","date_updated":"2025-09-04T13:04:34Z","page":"eadg6757","status":"public","scopus_import":"1","ec_funded":1,"issue":"6687","quality_controlled":"1","type":"journal_article","external_id":{"isi":["001216996700015"],"pmid":["38452088"]},"_id":"15117","abstract":[{"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.","lang":"eng"}],"language":[{"iso":"eng"}],"day":"08","citation":{"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>.","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>.","short":"D.H. Vandael, P.M. Jonas, Science 383 (2024) eadg6757.","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>"},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","year":"2024","intvolume":"       383","date_published":"2024-03-08T00:00:00Z","doi":"10.1126/science.adg6757","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.","department":[{"_id":"PeJo"}],"month":"03","article_type":"review","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"}],"volume":383,"author":[{"last_name":"Vandael","full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"}],"publisher":"AAAS","article_processing_charge":"No","corr_author":"1","pmid":1,"publication_status":"published","publication_identifier":{"eissn":["1095-9203"]},"oa_version":"None","title":"Structure, biophysics, and circuit function of a \"giant\" cortical presynaptic terminal","date_created":"2024-03-17T23:00:57Z"},{"oa_version":"Published Version","OA_type":"hybrid","title":"Imaging brain tissue architecture across millimeter to nanometer scales","date_created":"2023-09-03T22:01:15Z","publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"file":[{"file_name":"2024_NatureBiotech_Michalska.pdf","checksum":"57d5fafb16f02dcb9f7dddb1bd7e2a71","file_id":"18784","creator":"dernst","date_updated":"2025-01-09T07:48:01Z","relation":"main_file","access_level":"open_access","date_created":"2025-01-09T07:48:01Z","file_size":26065165,"success":1,"content_type":"application/pdf"}],"publication_status":"published","pmid":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"deleted","id":"18660"},{"relation":"research_data","status":"public","id":"13126"},{"relation":"dissertation_contains","status":"public","id":"18674"}],"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}]},"publisher":"Springer Nature","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"Yes (in subscription journal)","project":[{"grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232","name":"Molecular Drug Targets"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E","grant_number":"LS18-022"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"},{"grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry"}],"article_type":"original","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"month":"07","author":[{"full_name":"Michalska, Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","orcid":"0000-0003-3862-1235"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp"},{"full_name":"Korinkova, Hana","last_name":"Korinkova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","full_name":"Amberg, Nicole"},{"last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"full_name":"Höftberger, Romana","last_name":"Höftberger","first_name":"Romana"},{"orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","last_name":"Siegert","full_name":"Siegert, Sandra"},{"last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G"}],"volume":42,"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.).","doi":"10.1038/s41587-023-01911-8","oa":1,"date_published":"2024-07-01T00:00:00Z","OA_place":"publisher","year":"2024","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"intvolume":"        42","has_accepted_license":"1","day":"01","citation":{"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.","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.","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>.","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>","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.","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>","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>."},"type":"journal_article","quality_controlled":"1","_id":"14257","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"external_id":{"pmid":["37653226"],"isi":["001065254200001"]},"scopus_import":"1","ec_funded":1,"page":"1051-1064","status":"public","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"isi":1,"date_updated":"2026-04-14T08:34:35Z","publication":"Nature Biotechnology","file_date_updated":"2025-01-09T07:48:01Z"},{"abstract":[{"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.","lang":"eng"}],"_id":"18603","language":[{"iso":"eng"}],"external_id":{"isi":["001358568700003"],"pmid":["39556620"]},"type":"journal_article","quality_controlled":"1","has_accepted_license":"1","day":"18","citation":{"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>","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>.","short":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS Biology 22 (2024).","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.","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>.","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."},"intvolume":"        22","article_number":"e3002879","year":"2024","ddc":["570"],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2024-11-18T00:00:00Z","APC_amount":"6248,82 EUR","OA_place":"publisher","file_date_updated":"2024-12-03T08:56:53Z","date_updated":"2026-04-16T12:20:34Z","publication":"PLoS Biology","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"isi":1,"status":"public","ec_funded":1,"DOAJ_listed":"1","issue":"11","scopus_import":"1","publication_status":"published","file":[{"success":1,"content_type":"application/pdf","date_created":"2024-12-03T08:56:53Z","file_size":3057631,"access_level":"open_access","file_id":"18608","date_updated":"2024-12-03T08:56:53Z","relation":"main_file","creator":"dernst","checksum":"7de2dcb50deb65dde05c80082bb85a82","file_name":"2024_PloSBio_Kim.pdf"}],"publication_identifier":{"issn":["1544-9173"],"eissn":["1545-7885"]},"date_created":"2024-12-01T23:01:54Z","title":"Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons","oa_version":"Published Version","OA_type":"gold","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.","doi":"10.1371/journal.pbio.3002879","oa":1,"author":[{"orcid":"0000-0003-2344-1039","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena","full_name":"Kim, Olena","last_name":"Kim"},{"last_name":"Okamoto","full_name":"Okamoto, Yuji","id":"3337E116-F248-11E8-B48F-1D18A9856A87","first_name":"Yuji","orcid":"0000-0003-0408-6094"},{"last_name":"Kaufmann","full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","first_name":"Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Brose","full_name":"Brose, Nils","first_name":"Nils"},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M"}],"volume":22,"article_type":"original","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"},{"name":"Structural & functional basis of presynaptic plasticity","_id":"b1b85715-d554-11ed-a5ad-84a07fc9f18e","grant_number":"I06166"},{"grant_number":"W01205","call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit"},{"name":"FWF Open Access Fund","call_identifier":"FWF","_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1"}],"department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"month":"11","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"Yes","publisher":"Public Library of Science","pmid":1,"related_material":{"record":[{"id":"18296","status":"public","relation":"research_data"}]}},{"date_published":"2024-03-06T00:00:00Z","OA_place":"publisher","year":"2024","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"intvolume":"       112","has_accepted_license":"1","day":"06","citation":{"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>","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.","short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron 112 (2024) 755–771.e9.","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>.","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>","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."},"type":"journal_article","quality_controlled":"1","language":[{"iso":"eng"}],"_id":"14843","abstract":[{"lang":"eng","text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission."}],"external_id":{"pmid":["38215739"],"isi":["001202925700001"]},"scopus_import":"1","issue":"5","ec_funded":1,"status":"public","page":"755-771.e9","PlanS_conform":"1","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"isi":1,"date_updated":"2026-04-27T22:30:23Z","publication":"Neuron","file_date_updated":"2025-04-23T14:02:08Z","oa_version":"Published Version","OA_type":"hybrid","date_created":"2024-01-21T23:00:56Z","title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"file":[{"date_updated":"2025-04-23T14:02:08Z","file_id":"19614","creator":"dernst","relation":"main_file","file_name":"2024_Neuron_Chen.pdf","checksum":"30098b4f0209556ddfb3540a23d07ca5","file_size":8192355,"date_created":"2025-04-23T14:02:08Z","content_type":"application/pdf","success":1,"access_level":"open_access"}],"publication_status":"published","pmid":1,"related_material":{"record":[{"status":"public","id":"15101","relation":"dissertation_contains"}],"link":[{"url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/","relation":"press_release","description":"News on ISTA Website"}]},"publisher":"Elsevier","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","article_processing_charge":"Yes (via OA deal)","article_type":"original","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232"},{"_id":"26B66A3E-B435-11E9-9278-68D0E5697425","grant_number":"25383","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse"}],"department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"month":"03","volume":112,"author":[{"id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","first_name":"JingJing","last_name":"Chen","full_name":"Chen, JingJing"},{"last_name":"Kaufmann","full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","first_name":"Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, Chong","last_name":"Chen"},{"first_name":"Itaru","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","full_name":"Arai, Itaru","last_name":"Arai"},{"orcid":"0000-0003-2344-1039","first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","full_name":"Kim, Olena","last_name":"Kim"},{"orcid":"0000-0001-8761-9444","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"},{"full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"}],"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.","oa":1,"doi":"10.1016/j.neuron.2023.12.002"},{"related_material":{"record":[{"relation":"part_of_dissertation","id":"14843","status":"public"}]},"article_processing_charge":"No","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","publisher":"Institute of Science and Technology Austria","author":[{"full_name":"Chen, JingJing","last_name":"Chen","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","first_name":"JingJing"}],"department":[{"_id":"GradSch"},{"_id":"PeJo"}],"month":"03","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","_id":"26B66A3E-B435-11E9-9278-68D0E5697425","grant_number":"25383"}],"oa":1,"doi":"10.15479/at:ista:15101","degree_awarded":"PhD","alternative_title":["ISTA Thesis"],"date_created":"2024-03-11T10:09:54Z","title":"Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse","oa_version":"Published Version","publication_identifier":{"issn":["2663-337X"]},"file":[{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2024-03-11T14:10:58Z","file_size":11271363,"access_level":"closed","embargo_to":"open_access","date_updated":"2024-04-02T22:30:03Z","file_id":"15104","relation":"source_file","creator":"jchen","checksum":"db4947474ffa271e66c254b6fe876a55","file_name":"Thesis_Jingjing CHEN.docx"},{"access_level":"open_access","date_created":"2024-03-11T14:11:06Z","file_size":16627311,"content_type":"application/pdf","embargo":"2024-04-01","file_name":"Thesis_Jingjing CHEN_merged.pdf","checksum":"a5eeae8b5702cd540f5d03469bc33dde","relation":"main_file","file_id":"15105","date_updated":"2024-04-02T22:30:03Z","creator":"jchen"}],"supervisor":[{"full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"}],"publication_status":"published","ec_funded":1,"page":"84","status":"public","date_updated":"2026-04-07T13:24:22Z","acknowledged_ssus":[{"_id":"EM-Fac"}],"file_date_updated":"2024-04-02T22:30:03Z","OA_place":"publisher","date_published":"2024-03-11T00:00:00Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","ddc":["570"],"year":"2024","day":"11","citation":{"ieee":"J. Chen, “Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse,” Institute of Science and Technology Austria, 2024.","short":"J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science and Technology Austria, 2024.","mla":"Chen, JingJing. <i>Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>.","apa":"Chen, J. (2024). <i>Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>","ista":"Chen J. 2024. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria.","ama":"Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>","chicago":"Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>."},"has_accepted_license":"1","_id":"15101","abstract":[{"lang":"eng","text":"The coupling between presynaptic Ca2+ channels and release sensors is a key factor that\r\ndetermines speed and efficacy of synapse transmission. At some excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development, and tightening is often\r\nassociated with a switch in the reliance on different Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains unknown, and it is unclear how it changes\r\nduring development. To address this question, we analyzed the coupling configuration at the\r\ncerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of BC–PC indicated that release probability decreased, while the\r\nnumber of functional sites increased during development. Although transmitter release\r\npersistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic action potentials became shorter during development, suggesting reduced\r\nefficacy of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas docked vesicles were only clustered at later\r\ndevelopmental stages. The number of functional release sites correlated better with the AZ\r\nnumber early in development, but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling suggested a developmental transformation from a more random to a more\r\nclustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic\r\ntransmission."}],"language":[{"iso":"eng"}],"type":"dissertation"},{"article_processing_charge":"No","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"Public Library of Science","pmid":1,"doi":"10.1371/journal.pone.0277148","oa":1,"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).","author":[{"full_name":"Rothman, Jason Seth","last_name":"Rothman","first_name":"Jason Seth"},{"orcid":"0000-0003-0005-401X","first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane"},{"full_name":"Holderith, Noemi","last_name":"Holderith","first_name":"Noemi"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M"},{"first_name":"R.","full_name":"Angus Silver, R.","last_name":"Angus Silver"}],"volume":18,"department":[{"_id":"PeJo"}],"month":"03","article_type":"original","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Structural plasticity at mossy fiber-CA3 synapses","call_identifier":"FWF","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","grant_number":"V00739"}],"publication_identifier":{"eissn":["1932-6203"]},"title":"Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy","date_created":"2023-03-26T22:01:07Z","oa_version":"Published Version","publication_status":"published","file":[{"file_name":"2023_PLoSOne_Rothman.pdf","checksum":"2380331ec27cc87808826fc64419ac1c","date_updated":"2023-03-27T06:51:09Z","relation":"main_file","creator":"dernst","file_id":"12770","access_level":"open_access","file_size":7290413,"date_created":"2023-03-27T06:51:09Z","content_type":"application/pdf","success":1}],"status":"public","issue":"3 March","ec_funded":1,"scopus_import":"1","file_date_updated":"2023-03-27T06:51:09Z","date_updated":"2025-04-23T08:50:50Z","publication":"PLoS ONE","isi":1,"acknowledged_ssus":[{"_id":"EM-Fac"}],"article_number":"e0277148","intvolume":"        18","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"year":"2023","date_published":"2023-03-17T00:00:00Z","external_id":{"pmid":["36930689"],"isi":["001024737400001"]},"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"}],"_id":"12759","language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","citation":{"ama":"Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. <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>.","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>.","short":"J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver, PLoS ONE 18 (2023).","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>"},"day":"17","has_accepted_license":"1"},{"title":"Research data for the publication \"Imaging brain tissue architecture across millimeter to nanometer scales\"","date_created":"2023-06-07T07:15:12Z","oa_version":"Published 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","relation":"research_data","url":"https://pub.ista.ac.at/group_danzl/data/CATS/"}]},"oa":1,"doi":"10.15479/AT:ISTA:13126","acknowledgement":"We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr, Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger, Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for support with obtaining human samples. We gratefully acknowledge Eder Miguel for setting up webKnossos and Marek Šuplata for computational support and hardware control. We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing, imaging and optics, preclinical, and lab support facilities, and by the Library and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources: \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual Fellowship 101026635 under the EU Horizon 2020 program (JFW)","author":[{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G"}],"month":"08","department":[{"_id":"JoDa"},{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"Bio"},{"_id":"RySh"}],"project":[{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","grant_number":"LS18-022","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"},{"grant_number":"101026635","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["610"],"year":"2023","date_published":"2023-08-04T00:00:00Z","contributor":[{"first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik"},{"last_name":"Velicky","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Stefanickova"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer"},{"first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","last_name":"Amberg"},{"last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","orcid":"0000-0003-2356-9403"},{"first_name":"Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech"},{"first_name":"Romana","last_name":"Höftberger"},{"orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","last_name":"Siegert"},{"last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas"}],"_id":"13126","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here, we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"type":"research_data","day":"04","citation":{"mla":"Danzl, Johann G. <i>Research Data for the Publication “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.”</i> Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>.","short":"J.G. Danzl, (2023).","ieee":"J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales.’” Institute of Science and Technology Austria, 2023.","apa":"Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:13126\">https://doi.org/10.15479/AT:ISTA:13126</a>","ama":"Danzl JG. Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” 2023. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>","ista":"Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>.","chicago":"Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.’” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/AT:ISTA:13126\">https://doi.org/10.15479/AT:ISTA:13126</a>."},"has_accepted_license":"1","status":"public","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","ec_funded":1,"file_date_updated":"2023-08-04T13:19:47Z","date_updated":"2026-04-14T08:34:35Z","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}]},{"quality_controlled":"1","type":"journal_article","external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"_id":"13267","abstract":[{"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.","lang":"eng"}],"language":[{"iso":"eng"}],"citation":{"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>.","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.","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.","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>","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>","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.","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>."},"day":"01","has_accepted_license":"1","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2023","intvolume":"        20","OA_place":"publisher","date_published":"2023-08-01T00:00:00Z","file_date_updated":"2025-02-26T08:01:57Z","isi":1,"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"date_updated":"2026-04-07T12:58:30Z","publication":"Nature Methods","status":"public","page":"1256-1265","scopus_import":"1","ec_funded":1,"publication_status":"published","file":[{"content_type":"application/pdf","success":1,"file_size":14103039,"date_created":"2025-02-26T08:01:57Z","access_level":"open_access","relation":"main_file","date_updated":"2025-02-26T08:01:57Z","file_id":"19088","creator":"dernst","checksum":"a68e845780a82ea36d0d4d3212a87c10","file_name":"2023_NatureMethods_Velicky.pdf"}],"publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"OA_type":"hybrid","oa_version":"Published Version","title":"Dense 4D nanoscale reconstruction of living brain tissue","date_created":"2023-07-23T22:01:13Z","oa":1,"doi":"10.1038/s41592-023-01936-6","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.).","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"month":"08","project":[{"grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232","name":"Molecular Drug Targets"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E","grant_number":"LS18-022"},{"name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","_id":"24F9549A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715767"},{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry"},{"_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration"}],"article_type":"original","volume":20,"author":[{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","last_name":"Velicky"},{"first_name":"Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5665-0430","last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder"},{"full_name":"Michalska, Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","orcid":"0000-0003-3862-1235"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Wei, Donglai","last_name":"Wei","first_name":"Donglai"},{"first_name":"Zudi","full_name":"Lin, Zudi","last_name":"Lin"},{"full_name":"Watson, Jake","last_name":"Watson","orcid":"0000-0002-8698-3823","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"full_name":"Troidl, Jakob","last_name":"Troidl","first_name":"Jakob"},{"first_name":"Johanna","full_name":"Beyer, Johanna","last_name":"Beyer"},{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav"},{"orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0201-2315","last_name":"Jahr","full_name":"Jahr, Wiebke"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"last_name":"Grant","full_name":"Grant, Seth G.N.","first_name":"Seth G.N."},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia"},{"first_name":"Hanspeter","last_name":"Pfister","full_name":"Pfister, Hanspeter"},{"first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385","last_name":"Bickel","full_name":"Bickel, Bernd"},{"last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Springer Nature","article_processing_charge":"Yes (in subscription journal)","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","related_material":{"record":[{"relation":"research_data","id":"12817","status":"public"},{"relation":"shorter_version","status":"public","id":"14770"},{"status":"public","id":"11943","relation":"earlier_version"},{"relation":"dissertation_contains","status":"public","id":"18674"}],"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}]},"pmid":1},{"publication_status":"published","file":[{"file_id":"11990","relation":"main_file","creator":"dernst","date_updated":"2022-08-26T11:51:40Z","checksum":"405936d9e4d33625d80c093c9713a91f","file_name":"2022_NatureCommunications_BenSimon.pdf","content_type":"application/pdf","success":1,"date_created":"2022-08-26T11:51:40Z","file_size":5910357,"access_level":"open_access"}],"publication_identifier":{"issn":["2041-1723"]},"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"oa_version":"Published Version","title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","date_created":"2022-08-24T08:25:50Z","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.).","doi":"10.1038/s41467-022-32559-8","oa":1,"article_type":"original","project":[{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"month":"08","volume":13,"author":[{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav"},{"full_name":"Käfer, Karola","last_name":"Käfer","first_name":"Karola","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","last_name":"Velicky","full_name":"Velicky, Philipp"},{"full_name":"Csicsvari, Jozsef L","last_name":"Csicsvari","orcid":"0000-0002-5193-4036","first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"}],"publisher":"Springer Nature","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","article_processing_charge":"No","pmid":1,"type":"journal_article","quality_controlled":"1","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"}],"_id":"11951","language":[{"iso":"eng"}],"external_id":{"pmid":["35974109"],"isi":["000841396400008"]},"has_accepted_license":"1","day":"16","citation":{"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>","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>.","short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022).","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.","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>.","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."},"year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"article_number":"4826","intvolume":"        13","date_published":"2022-08-16T00:00:00Z","file_date_updated":"2022-08-26T11:51:40Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"isi":1,"publication":"Nature Communications","date_updated":"2025-06-12T06:10:44Z","status":"public","scopus_import":"1","ec_funded":1},{"type":"journal_article","quality_controlled":"1","_id":"12288","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"}],"language":[{"iso":"eng"}],"external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"has_accepted_license":"1","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>","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.","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>.","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).","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.","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>"},"day":"15","year":"2022","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":"        11","article_number":"79848","date_published":"2022-09-15T00:00:00Z","file_date_updated":"2023-01-30T11:50:53Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"isi":1,"publication":"eLife","date_updated":"2025-04-15T08:29:05Z","status":"public","scopus_import":"1","ec_funded":1,"publication_status":"published","file":[{"content_type":"application/pdf","success":1,"date_created":"2023-01-30T11:50:53Z","file_size":8506811,"access_level":"open_access","file_id":"12463","date_updated":"2023-01-30T11:50:53Z","creator":"dernst","relation":"main_file","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","file_name":"2022_eLife_Sumser.pdf"}],"publication_identifier":{"eissn":["2050-084X"]},"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"oa_version":"Published Version","title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","date_created":"2023-01-16T10:04:15Z","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).","oa":1,"doi":"10.7554/elife.79848","article_type":"original","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Circuits of Visual Attention","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"756502"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits"},{"name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425","grant_number":"LT000256"},{"name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1098-2017"}],"department":[{"_id":"MaJö"},{"_id":"PeJo"}],"month":"09","volume":11,"author":[{"full_name":"Sumser, Anton L","last_name":"Sumser","orcid":"0000-0002-4792-1881","first_name":"Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jösch","full_name":"Jösch, Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","first_name":"Maximilian A","orcid":"0000-0002-3937-1330"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M"},{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"}],"publisher":"eLife Sciences Publications","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"No","pmid":1},{"file_date_updated":"2023-04-20T22:30:03Z","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"date_updated":"2026-04-07T14:22:20Z","page":"132","status":"public","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"type":"dissertation","language":[{"iso":"eng"}],"_id":"11196","abstract":[{"text":"One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.\r\n","lang":"eng"}],"citation":{"chicago":"Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11196\">https://doi.org/10.15479/at:ista:11196</a>.","ama":"Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11196\">10.15479/at:ista:11196</a>","ista":"Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria.","apa":"Kim, O. (2022). <i>Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11196\">https://doi.org/10.15479/at:ista:11196</a>","mla":"Kim, Olena. <i>Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11196\">10.15479/at:ista:11196</a>.","ieee":"O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022.","short":"O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022."},"day":"20","has_accepted_license":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","ddc":["570"],"year":"2022","OA_place":"publisher","date_published":"2022-04-20T00:00:00Z","doi":"10.15479/at:ista:11196","oa":1,"degree_awarded":"PhD","department":[{"_id":"PeJo"},{"_id":"GradSch"}],"month":"04","project":[{"grant_number":"708497","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse"},{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"}],"author":[{"last_name":"Kim","full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena","orcid":"0000-0003-2344-1039"}],"publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"corr_author":"1","related_material":{"record":[{"status":"public","id":"7473","relation":"part_of_dissertation"},{"status":"public","id":"11222","relation":"part_of_dissertation"}]},"publication_status":"published","supervisor":[{"last_name":"Jonas","full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"}],"file":[{"embargo":"2023-04-19","relation":"main_file","file_id":"11220","date_updated":"2023-04-20T22:30:03Z","creator":"okim","file_name":"Olena_KIM_thesis_final.pdf","checksum":"1616a8bf6f13a57c892dac873dcd0936","date_created":"2022-04-20T14:21:56Z","file_size":21273537,"content_type":"application/pdf","access_level":"open_access"},{"creator":"okim","date_updated":"2023-04-20T22:30:03Z","relation":"source_file","file_id":"11221","checksum":"1acb433f98dc42abb0b4b0cbb0c4b918","file_name":"KIM_thesis_final.zip","embargo_to":"open_access","content_type":"application/x-zip-compressed","date_created":"2022-04-20T14:22:56Z","file_size":59248569,"access_level":"closed"}],"publication_identifier":{"issn":["2663-337X"]},"oa_version":"Published Version","date_created":"2022-04-20T09:47:12Z","title":"Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses","alternative_title":["ISTA Thesis"]},{"status":"public","scopus_import":"1","ec_funded":1,"issue":"6","file_date_updated":"2021-04-19T08:30:22Z","acknowledged_ssus":[{"_id":"SSU"}],"isi":1,"date_updated":"2025-06-12T06:39:15Z","publication":"Journal of Neuroscience Methods","year":"2021","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"intvolume":"       357","article_number":"109125","date_published":"2021-03-09T00:00:00Z","type":"journal_article","quality_controlled":"1","_id":"9329","abstract":[{"lang":"eng","text":"Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.\r\nNew method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.\r\nResults: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.\r\nComparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.\r\nConclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity."}],"language":[{"iso":"eng"}],"external_id":{"pmid":["33711356"],"isi":["000661088500005"]},"has_accepted_license":"1","citation":{"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.","short":"X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (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>.","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.","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>"},"day":"09","publisher":"Elsevier","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"article_processing_charge":"Yes (via OA deal)","pmid":1,"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.","oa":1,"doi":"10.1016/j.jneumeth.2021.109125","article_type":"original","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312"}],"month":"03","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"author":[{"id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","full_name":"Zhang, Xiaomin","last_name":"Zhang"},{"full_name":"Schlögl, Alois","last_name":"Schlögl","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5621-8100"},{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","orcid":"0000-0001-7577-1676","last_name":"Vandael","full_name":"Vandael, David H"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M"}],"volume":357,"publication_identifier":{"issn":["0165-0270"],"eissn":["1872-678X"]},"oa_version":"Published Version","title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","date_created":"2021-04-18T22:01:39Z","publication_status":"published","file":[{"content_type":"application/pdf","success":1,"file_size":6924738,"date_created":"2021-04-19T08:30:22Z","access_level":"open_access","creator":"dernst","relation":"main_file","date_updated":"2021-04-19T08:30:22Z","file_id":"9339","checksum":"2a5800d91b96d08b525e17319dcd5e44","file_name":"2021_JourNeuroscienceMeth_Zhang.pdf"}]},{"doi":"10.1038/s41467-021-23153-5","oa":1,"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.","month":"05","department":[{"_id":"PeJo"}],"article_type":"original","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"volume":12,"author":[{"first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","last_name":"Vandael","full_name":"Vandael, David H"},{"last_name":"Okamoto","full_name":"Okamoto, Yuji","orcid":"0000-0003-0408-6094","id":"3337E116-F248-11E8-B48F-1D18A9856A87","first_name":"Yuji"},{"full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"}],"publisher":"Springer","article_processing_charge":"Yes","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"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/"}]},"pmid":1,"publication_status":"published","file":[{"date_created":"2021-12-17T11:34:50Z","file_size":3108845,"success":1,"content_type":"application/pdf","access_level":"open_access","creator":"kschuh","date_updated":"2021-12-17T11:34:50Z","file_id":"10563","relation":"main_file","file_name":"2021_NatureCommunications_Vandael.pdf","checksum":"6036a8cdae95e1707c2a04d54e325ff4"}],"keyword":["general physics and astronomy","general biochemistry","genetics and molecular biology","general chemistry"],"publication_identifier":{"issn":["2041-1723"]},"OA_type":"gold","oa_version":"Published Version","title":"Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses","date_created":"2021-08-06T07:22:55Z","file_date_updated":"2021-12-17T11:34:50Z","isi":1,"acknowledged_ssus":[{"_id":"SSU"}],"publication":"Nature Communications","date_updated":"2025-06-12T06:28:45Z","status":"public","scopus_import":"1","ec_funded":1,"issue":"1","quality_controlled":"1","type":"journal_article","external_id":{"isi":["000655481800014"],"pmid":["34006874"]},"language":[{"iso":"eng"}],"_id":"9778","abstract":[{"lang":"eng","text":"The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses."}],"day":"18","citation":{"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>","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>.","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>.","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.","short":"D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021).","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>"},"has_accepted_license":"1","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2021","intvolume":"        12","article_number":"2912","OA_place":"publisher","date_published":"2021-05-18T00:00:00Z"},{"department":[{"_id":"HeEd"}],"month":"06","project":[{"name":"Alpha Shape Theory Extended","grant_number":"788183","_id":"266A2E9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Persistent Homology, Algorithms and Stochastic Geometry","_id":"0aa4bc98-070f-11eb-9043-e6fff9c6a316","grant_number":"I4887"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"}],"author":[{"last_name":"Edelsbrunner","full_name":"Edelsbrunner, Herbert","orcid":"0000-0002-9823-6833","id":"3FB178DA-F248-11E8-B48F-1D18A9856A87","first_name":"Herbert"},{"full_name":"Heiss, Teresa","last_name":"Heiss","first_name":"Teresa","id":"4879BB4E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1780-2689"},{"last_name":" Kurlin ","full_name":" Kurlin , Vitaliy","first_name":"Vitaliy"},{"last_name":"Smith","full_name":"Smith, Philip","first_name":"Philip"},{"orcid":"0000-0002-7472-2220","first_name":"Mathijs","id":"307CFBC8-F248-11E8-B48F-1D18A9856A87","last_name":"Wintraecken","full_name":"Wintraecken, Mathijs"}],"volume":189,"oa":1,"doi":"10.4230/LIPIcs.SoCG.2021.32","acknowledgement":"The authors thank Janos Pach for insightful discussions on the topic of thispaper, Morteza Saghafian for finding the one-dimensional counterexample mentioned in Section 5,and Larry Andrews for generously sharing his crystallographic perspective.","related_material":{"record":[{"relation":"dissertation_contains","id":"18667","status":"public"}]},"publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","article_processing_charge":"No","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"file":[{"creator":"mwintrae","file_id":"9346","date_updated":"2021-04-22T08:08:14Z","relation":"main_file","checksum":"1787baef1523d6d93753b90d0c109a6d","file_name":"df_socg_final_version.pdf","content_type":"application/pdf","success":1,"file_size":3117435,"date_created":"2021-04-22T08:08:14Z","access_level":"open_access"}],"conference":{"end_date":"2021-06-11","location":"Virtual","name":"SoCG: Symposium on Computational Geometry","start_date":"2021-06-07"},"publication_status":"published","oa_version":"Published Version","title":"The density fingerprint of a periodic point set","date_created":"2021-04-22T08:09:58Z","alternative_title":["LIPIcs"],"publication_identifier":{"issn":["1868-8969"]},"publication":"37th International Symposium on Computational Geometry (SoCG 2021)","date_updated":"2026-04-07T12:54:09Z","file_date_updated":"2021-04-22T08:08:14Z","scopus_import":"1","ec_funded":1,"page":"32:1-32:16","status":"public","day":"02","citation":{"apa":"Edelsbrunner, H., Heiss, T.,  Kurlin , V., Smith, P., &#38; Wintraecken, M. (2021). The density fingerprint of a periodic point set. In <i>37th International Symposium on Computational Geometry (SoCG 2021)</i> (Vol. 189, p. 32:1-32:16). Virtual: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. <a href=\"https://doi.org/10.4230/LIPIcs.SoCG.2021.32\">https://doi.org/10.4230/LIPIcs.SoCG.2021.32</a>","short":"H. Edelsbrunner, T. Heiss, V.  Kurlin , P. Smith, M. Wintraecken, in:, 37th International Symposium on Computational Geometry (SoCG 2021), Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2021, p. 32:1-32:16.","ieee":"H. Edelsbrunner, T. Heiss, V.  Kurlin , P. Smith, and M. Wintraecken, “The density fingerprint of a periodic point set,” in <i>37th International Symposium on Computational Geometry (SoCG 2021)</i>, Virtual, 2021, vol. 189, p. 32:1-32:16.","mla":"Edelsbrunner, Herbert, et al. “The Density Fingerprint of a Periodic Point Set.” <i>37th International Symposium on Computational Geometry (SoCG 2021)</i>, vol. 189, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2021, p. 32:1-32:16, doi:<a href=\"https://doi.org/10.4230/LIPIcs.SoCG.2021.32\">10.4230/LIPIcs.SoCG.2021.32</a>.","chicago":"Edelsbrunner, Herbert, Teresa Heiss, Vitaliy  Kurlin , Philip Smith, and Mathijs Wintraecken. “The Density Fingerprint of a Periodic Point Set.” In <i>37th International Symposium on Computational Geometry (SoCG 2021)</i>, 189:32:1-32:16. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2021. <a href=\"https://doi.org/10.4230/LIPIcs.SoCG.2021.32\">https://doi.org/10.4230/LIPIcs.SoCG.2021.32</a>.","ista":"Edelsbrunner H, Heiss T,  Kurlin  V, Smith P, Wintraecken M. 2021. The density fingerprint of a periodic point set. 37th International Symposium on Computational Geometry (SoCG 2021). SoCG: Symposium on Computational Geometry, LIPIcs, vol. 189, 32:1-32:16.","ama":"Edelsbrunner H, Heiss T,  Kurlin  V, Smith P, Wintraecken M. The density fingerprint of a periodic point set. In: <i>37th International Symposium on Computational Geometry (SoCG 2021)</i>. Vol 189. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2021:32:1-32:16. doi:<a href=\"https://doi.org/10.4230/LIPIcs.SoCG.2021.32\">10.4230/LIPIcs.SoCG.2021.32</a>"},"has_accepted_license":"1","quality_controlled":"1","type":"conference","language":[{"iso":"eng"}],"_id":"9345","abstract":[{"text":"Modeling a crystal as a periodic point set, we present a fingerprint consisting of density functionsthat facilitates the efficient search for new materials and material properties. We prove invarianceunder isometries, continuity, and completeness in the generic case, which are necessary featuresfor the reliable comparison of crystals. The proof of continuity integrates methods from discretegeometry and lattice theory, while the proof of generic completeness combines techniques fromgeometry with analysis. The fingerprint has a fast algorithm based on Brillouin zones and relatedinclusion-exclusion formulae. We have implemented the algorithm and describe its application tocrystal structure prediction.","lang":"eng"}],"date_published":"2021-06-02T00:00:00Z","user_id":"D865714E-FA4E-11E9-B85B-F5C5E5697425","ddc":["004","516"],"year":"2021","intvolume":"       189"},{"author":[{"full_name":"Guzmán, José","last_name":"Guzmán","orcid":"0000-0003-2209-5242","id":"30CC5506-F248-11E8-B48F-1D18A9856A87","first_name":"José"},{"first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5621-8100","last_name":"Schlögl","full_name":"Schlögl, Alois"},{"last_name":"Espinoza Martinez","full_name":"Espinoza Martinez, Claudia ","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia ","orcid":"0000-0003-4710-2082"},{"full_name":"Zhang, Xiaomin","last_name":"Zhang","orcid":"0000-0003-0256-6529","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin"},{"first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9885-6936","last_name":"Suter","full_name":"Suter, Benjamin"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"}],"volume":1,"article_type":"original","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312"}],"month":"12","department":[{"_id":"PeJo"}],"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.).","doi":"10.1038/s43588-021-00157-1","oa":1,"related_material":{"record":[{"relation":"software","status":"public","id":"10110"}],"link":[{"url":"https://ista.ac.at/en/news/spot-the-difference/","relation":"press_release"}]},"corr_author":"1","article_processing_charge":"No","publisher":"Springer Nature","file":[{"access_level":"open_access","date_created":"2022-06-02T12:51:07Z","file_size":1699466,"content_type":"application/pdf","embargo":"2022-06-17","file_name":"Guzmanetal2021.pdf","checksum":"9fec5b667909ef52be96d502e4f8c2ae","date_updated":"2022-06-18T22:30:03Z","file_id":"11430","relation":"main_file","creator":"patrickd"},{"title":"Supplementary Material","file_size":3005651,"date_created":"2022-06-02T12:53:47Z","content_type":"application/pdf","access_level":"open_access","embargo":"2022-06-17","date_updated":"2022-06-18T22:30:03Z","file_id":"11431","relation":"supplementary_material","creator":"patrickd","file_name":"Guzmanetal2021Suppl.pdf","checksum":"52a005b13a114e3c3a28fa6bbe8b1a8d"}],"publication_status":"published","date_created":"2022-03-04T08:32:36Z","title":"How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network","oa_version":"Submitted Version","publication_identifier":{"issn":["2662-8457"]},"keyword":["general medicine"],"date_updated":"2025-10-09T22:30:54Z","publication":"Nature Computational Science","acknowledged_ssus":[{"_id":"SSU"}],"isi":1,"file_date_updated":"2022-06-18T22:30:03Z","issue":"12","ec_funded":1,"scopus_import":"1","status":"public","page":"830-842","has_accepted_license":"1","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>","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.","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>.","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.","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.","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>"},"day":"16","_id":"10816","language":[{"iso":"eng"}],"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."}],"external_id":{"isi":["000888567500015"]},"type":"journal_article","quality_controlled":"1","date_published":"2021-12-16T00:00:00Z","main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/647800"}],"intvolume":"         1","year":"2021","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","ddc":["610"]},{"ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2021","intvolume":"        16","date_published":"2021-06-01T00:00:00Z","quality_controlled":"1","type":"journal_article","external_id":{"isi":["000650528700003"],"pmid":["33990799"]},"language":[{"iso":"eng"}],"_id":"9438","abstract":[{"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.","lang":"eng"}],"day":"01","citation":{"ama":"Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. <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>","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.","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>.","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>.","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.","short":"D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.","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>"},"has_accepted_license":"1","status":"public","page":"2947–2967","scopus_import":"1","issue":"6","ec_funded":1,"file_date_updated":"2021-12-02T23:30:05Z","isi":1,"acknowledged_ssus":[{"_id":"M-Shop"}],"date_updated":"2025-04-22T22:30:43Z","publication":"Nature Protocols","publication_identifier":{"issn":["1754-2189"],"eissn":["1750-2799"]},"oa_version":"Submitted Version","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","publication_status":"published","file":[{"content_type":"application/pdf","date_created":"2021-07-08T12:27:55Z","file_size":38574802,"access_level":"open_access","date_updated":"2021-12-02T23:30:05Z","creator":"cziletti","relation":"main_file","file_id":"9639","checksum":"7eb580abd8893cdb0b410cf41bc8c263","file_name":"VandaeletalAuthorVersion2021.pdf","embargo":"2021-12-01"}],"publisher":"Springer Nature","article_processing_charge":"No","corr_author":"1","pmid":1,"doi":"10.1038/s41596-021-00526-0","oa":1,"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.","department":[{"_id":"PeJo"}],"month":"06","article_type":"original","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","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"}],"author":[{"first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","last_name":"Vandael","full_name":"Vandael, David H"},{"last_name":"Okamoto","full_name":"Okamoto, Yuji","id":"3337E116-F248-11E8-B48F-1D18A9856A87","first_name":"Yuji","orcid":"0000-0003-0408-6094"},{"full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina"},{"id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M","full_name":"Vargas Barroso, Victor M","last_name":"Vargas Barroso"},{"full_name":"Suter, Benjamin","last_name":"Suter","orcid":"0000-0002-9885-6936","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","first_name":"Benjamin"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"}],"volume":16},{"publication_status":"published","file":[{"date_created":"2020-11-25T11:23:02Z","file_size":4390833,"content_type":"application/pdf","success":1,"access_level":"open_access","creator":"dernst","relation":"main_file","file_id":"8811","date_updated":"2020-11-25T11:23:02Z","file_name":"2020_Neuron_Vandael.pdf","checksum":"4030b2be0c9625d54694a1e9fb00305e"}],"publication_identifier":{"issn":["0896-6273"],"eissn":["10974199"]},"title":"Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation","date_created":"2020-06-22T13:29:05Z","oa_version":"Published Version","acknowledgement":"This project received funding from the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Program (grant agreement 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung ( Z 312-B27 , Wittgenstein award to P.J. and V 739-B27 to C.B.-M.). We thank Drs. Jozsef Csicsvari, Jose Guzman, Erwin Neher, and Ryuichi Shigemoto for commenting on earlier versions of the manuscript. We are grateful to Walter Kaufmann, Daniel Gütl, and Vanessa Zheden for EM training; Alois Schlögl for programming; Florian Marr for excellent technical assistance and cell reconstruction; Christina Altmutter for technical help; Eleftheria Kralli-Beller for manuscript editing; Taija Makinen for providing the Prox1-CreERT2 mouse line; and the Scientific Service Units of IST Austria for support.","oa":1,"doi":"10.1016/j.neuron.2020.05.013","author":[{"orcid":"0000-0001-7577-1676","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","full_name":"Vandael, David H","last_name":"Vandael"},{"full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane","first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0005-401X"},{"id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","last_name":"Zhang","full_name":"Zhang, Xiaomin"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M"}],"volume":107,"article_type":"original","project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"grant_number":"V00739","call_identifier":"FWF","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","name":"Structural plasticity at mossy fiber-CA3 synapses"}],"month":"08","department":[{"_id":"PeJo"}],"tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"corr_author":"1","article_processing_charge":"No","publisher":"Elsevier","pmid":1,"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/possible-physical-trace-of-short-term-memory-found/"}]},"_id":"8001","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network."}],"external_id":{"pmid":["32492366"],"isi":["000556135600004"]},"type":"journal_article","quality_controlled":"1","has_accepted_license":"1","day":"05","citation":{"ista":"Vandael DH, Borges Merjane C, Zhang X, Jonas PM. 2020. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. 107(3), 509–521.","ama":"Vandael DH, Borges Merjane C, Zhang X, Jonas PM. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. <i>Neuron</i>. 2020;107(3):509-521. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">10.1016/j.neuron.2020.05.013</a>","chicago":"Vandael, David H, Carolina Borges Merjane, Xiaomin Zhang, and Peter M Jonas. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">https://doi.org/10.1016/j.neuron.2020.05.013</a>.","short":"D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020) 509–521.","ieee":"D. H. Vandael, C. Borges Merjane, X. Zhang, and P. M. Jonas, “Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation,” <i>Neuron</i>, vol. 107, no. 3. Elsevier, pp. 509–521, 2020.","mla":"Vandael, David H., et al. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” <i>Neuron</i>, vol. 107, no. 3, Elsevier, 2020, pp. 509–21, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">10.1016/j.neuron.2020.05.013</a>.","apa":"Vandael, D. H., Borges Merjane, C., Zhang, X., &#38; Jonas, P. M. (2020). Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">https://doi.org/10.1016/j.neuron.2020.05.013</a>"},"intvolume":"       107","year":"2020","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"date_published":"2020-08-05T00:00:00Z","file_date_updated":"2020-11-25T11:23:02Z","publication":"Neuron","date_updated":"2025-04-15T08:29:09Z","acknowledged_ssus":[{"_id":"SSU"}],"isi":1,"page":"509-521","status":"public","issue":"3","ec_funded":1,"scopus_import":"1"},{"author":[{"id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","full_name":"Zhang, Xiaomin","last_name":"Zhang"},{"full_name":"Schlögl, Alois","last_name":"Schlögl","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5621-8100"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M"}],"volume":107,"month":"09","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"article_type":"original","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"}],"oa":1,"doi":"10.1016/j.neuron.2020.07.006","acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari, Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp recording. We are grateful to Florian Marr for cell labeling, cell reconstruction, and technical assistance; Ben Suter for helpful discussions; Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor Asenov (Machine Shop) for device construction. We also thank the Scientific Service Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical Facility) for efficient support.","related_material":{"link":[{"relation":"press_release","description":"News on IST Website","url":"https://ist.ac.at/en/news/the-bouncer-in-the-brain/"}]},"pmid":1,"article_processing_charge":"No","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"corr_author":"1","publisher":"Elsevier","file":[{"file_name":"2020_Neuron_Zhang.pdf","checksum":"44a5960fc083a4cb3488d22224859fdc","relation":"main_file","file_id":"8920","date_updated":"2020-12-04T09:29:21Z","creator":"dernst","access_level":"open_access","date_created":"2020-12-04T09:29:21Z","file_size":3011120,"content_type":"application/pdf","success":1}],"publication_status":"published","date_created":"2020-08-14T09:36:05Z","title":"Selective routing of spatial information flow from input to output in hippocampal granule cells","oa_version":"Published Version","publication_identifier":{"issn":["0896-6273"]},"date_updated":"2025-04-15T08:29:03Z","publication":"Neuron","isi":1,"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"ScienComp"},{"_id":"PreCl"}],"file_date_updated":"2020-12-04T09:29:21Z","issue":"6","ec_funded":1,"scopus_import":"1","status":"public","page":"1212-1225","day":"23","citation":{"short":"X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225.","ieee":"X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information flow from input to output in hippocampal granule cells,” <i>Neuron</i>, vol. 107, no. 6. Elsevier, pp. 1212–1225, 2020.","mla":"Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” <i>Neuron</i>, vol. 107, no. 6, Elsevier, 2020, pp. 1212–25, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">10.1016/j.neuron.2020.07.006</a>.","apa":"Zhang, X., Schlögl, A., &#38; Jonas, P. M. (2020). Selective routing of spatial information flow from input to output in hippocampal granule cells. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">https://doi.org/10.1016/j.neuron.2020.07.006</a>","ista":"Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. 107(6), 1212–1225.","ama":"Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow from input to output in hippocampal granule cells. <i>Neuron</i>. 2020;107(6):1212-1225. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">10.1016/j.neuron.2020.07.006</a>","chicago":"Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.07.006\">https://doi.org/10.1016/j.neuron.2020.07.006</a>."},"has_accepted_license":"1","external_id":{"pmid":["32763145"],"isi":["000579698700009"]},"_id":"8261","abstract":[{"lang":"eng","text":"Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion."}],"language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","date_published":"2020-09-23T00:00:00Z","intvolume":"       107","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","year":"2020"},{"doi":"10.29007/7dt2","oa":1,"acknowledgement":"The authors gratefully acknowledge financial support by the European Commission project\r\njustITSELF under grant number 817629, by the Austrian Science Fund (FWF) under grant\r\nZ211-N23 (Wittgenstein Award), by the European Union’s Horizon 2020 research and innovation programme under the Marie Sk lodowska-Curie grant agreement No. 754411, and by the\r\nScience and Engineering Research Board (SERB) project with file number IMP/2018/000523.\r\nThis material is based upon work supported by the Air Force Office of Scientific Research under\r\naward number FA9550-19-1-0288. Any opinions, finding, and conclusions or recommendations\r\nexpressed in this material are those of the author(s) and do not necessarily reflect the views of\r\nthe United States Air Force.","month":"09","department":[{"_id":"ToHe"}],"project":[{"name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312"},{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"volume":74,"author":[{"last_name":"Althoff","full_name":"Althoff, Matthias","first_name":"Matthias"},{"first_name":"Stanley","last_name":"Bak","full_name":"Bak, Stanley"},{"first_name":"Zongnan","last_name":"Bao","full_name":"Bao, Zongnan"},{"first_name":"Marcelo","full_name":"Forets, Marcelo","last_name":"Forets"},{"last_name":"Frehse","full_name":"Frehse, Goran","first_name":"Goran"},{"first_name":"Daniel","full_name":"Freire, Daniel","last_name":"Freire"},{"full_name":"Kochdumper, Niklas","last_name":"Kochdumper","first_name":"Niklas"},{"full_name":"Li, Yangge","last_name":"Li","first_name":"Yangge"},{"first_name":"Sayan","last_name":"Mitra","full_name":"Mitra, Sayan"},{"first_name":"Rajarshi","full_name":"Ray, Rajarshi","last_name":"Ray"},{"last_name":"Schilling","full_name":"Schilling, Christian","id":"3A2F4DCE-F248-11E8-B48F-1D18A9856A87","first_name":"Christian","orcid":"0000-0003-3658-1065"},{"full_name":"Schupp, Stefan","last_name":"Schupp","first_name":"Stefan"},{"last_name":"Wetzlinger","full_name":"Wetzlinger, Mark","first_name":"Mark"}],"publisher":"EasyChair","article_processing_charge":"No","corr_author":"1","conference":{"name":"ARCH: International Workshop on Applied Verification on Continuous and Hybrid Systems","start_date":"2020-07-12","end_date":"2020-07-12"},"publication_status":"published","oa_version":"Published Version","date_created":"2020-09-26T14:49:43Z","title":"ARCH-COMP20 Category Report: Continuous and hybrid systems with linear dynamics","publication":"EPiC Series in Computing","date_updated":"2025-04-15T08:29:04Z","page":"16-48","status":"public","scopus_import":"1","ec_funded":1,"quality_controlled":"1","type":"conference","abstract":[{"text":"We present the results of the ARCH 2020 friendly competition for formal verification of continuous and hybrid systems with linear continuous dynamics. In its fourth edition, eight tools have been applied to solve eight different benchmark problems in the category for linear continuous dynamics (in alphabetical order): CORA, C2E2, HyDRA, Hylaa, Hylaa-Continuous, JuliaReach, SpaceEx, and XSpeed. This report is a snapshot of the current landscape of tools and the types of benchmarks they are particularly suited for. Due to the diversity of problems, we are not ranking tools, yet the presented results provide one of the most complete assessments of tools for the safety verification of continuous and hybrid systems with linear continuous dynamics up to this date.","lang":"eng"}],"_id":"8572","language":[{"iso":"eng"}],"citation":{"short":"M. Althoff, S. Bak, Z. Bao, M. Forets, G. Frehse, D. Freire, N. Kochdumper, Y. Li, S. Mitra, R. Ray, C. Schilling, S. Schupp, M. Wetzlinger, in:, EPiC Series in Computing, EasyChair, 2020, pp. 16–48.","ieee":"M. Althoff <i>et al.</i>, “ARCH-COMP20 Category Report: Continuous and hybrid systems with linear dynamics,” in <i>EPiC Series in Computing</i>, 2020, vol. 74, pp. 16–48.","mla":"Althoff, Matthias, et al. “ARCH-COMP20 Category Report: Continuous and Hybrid Systems with Linear Dynamics.” <i>EPiC Series in Computing</i>, vol. 74, EasyChair, 2020, pp. 16–48, doi:<a href=\"https://doi.org/10.29007/7dt2\">10.29007/7dt2</a>.","apa":"Althoff, M., Bak, S., Bao, Z., Forets, M., Frehse, G., Freire, D., … Wetzlinger, M. (2020). ARCH-COMP20 Category Report: Continuous and hybrid systems with linear dynamics. In <i>EPiC Series in Computing</i> (Vol. 74, pp. 16–48). EasyChair. <a href=\"https://doi.org/10.29007/7dt2\">https://doi.org/10.29007/7dt2</a>","ista":"Althoff M, Bak S, Bao Z, Forets M, Frehse G, Freire D, Kochdumper N, Li Y, Mitra S, Ray R, Schilling C, Schupp S, Wetzlinger M. 2020. ARCH-COMP20 Category Report: Continuous and hybrid systems with linear dynamics. EPiC Series in Computing. ARCH: International Workshop on Applied Verification on Continuous and Hybrid Systems vol. 74, 16–48.","ama":"Althoff M, Bak S, Bao Z, et al. ARCH-COMP20 Category Report: Continuous and hybrid systems with linear dynamics. In: <i>EPiC Series in Computing</i>. Vol 74. EasyChair; 2020:16-48. doi:<a href=\"https://doi.org/10.29007/7dt2\">10.29007/7dt2</a>","chicago":"Althoff, Matthias, Stanley Bak, Zongnan Bao, Marcelo Forets, Goran Frehse, Daniel Freire, Niklas Kochdumper, et al. “ARCH-COMP20 Category Report: Continuous and Hybrid Systems with Linear Dynamics.” In <i>EPiC Series in Computing</i>, 74:16–48. EasyChair, 2020. <a href=\"https://doi.org/10.29007/7dt2\">https://doi.org/10.29007/7dt2</a>."},"day":"25","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2020","intvolume":"        74","main_file_link":[{"url":"https://easychair.org/publications/download/DRpS","open_access":"1"}],"date_published":"2020-09-25T00:00:00Z"},{"_id":"8287","abstract":[{"text":"Reachability analysis aims at identifying states reachable by a system within a given time horizon. This task is known to be computationally expensive for linear hybrid systems. Reachability analysis works by iteratively applying continuous and discrete post operators to compute states reachable according to continuous and discrete dynamics, respectively. In this paper, we enhance both of these operators and make sure that most of the involved computations are performed in low-dimensional state space. In particular, we improve the continuous-post operator by performing computations in high-dimensional state space only for time intervals relevant for the subsequent application of the discrete-post operator. Furthermore, the new discrete-post operator performs low-dimensional computations by leveraging the structure of the guard and assignment of a considered transition. We illustrate the potential of our approach on a number of challenging benchmarks.","lang":"eng"}],"language":[{"iso":"eng"}],"external_id":{"arxiv":["1905.02458"],"isi":["000587712700072"]},"type":"conference","quality_controlled":"1","has_accepted_license":"1","day":"01","citation":{"short":"S. Bogomolov, M. Forets, G. Frehse, K. Potomkin, C. Schilling, in:, Proceedings of the International Conference on Embedded Software, 2020.","ieee":"S. Bogomolov, M. Forets, G. Frehse, K. Potomkin, and C. Schilling, “Reachability analysis of linear hybrid systems via block decomposition,” in <i>Proceedings of the International Conference on Embedded Software</i>, Virtual , 2020.","mla":"Bogomolov, Sergiy, et al. “Reachability Analysis of Linear Hybrid Systems via Block Decomposition.” <i>Proceedings of the International Conference on Embedded Software</i>, 2020.","apa":"Bogomolov, S., Forets, M., Frehse, G., Potomkin, K., &#38; Schilling, C. (2020). Reachability analysis of linear hybrid systems via block decomposition. In <i>Proceedings of the International Conference on Embedded Software</i>. Virtual .","ista":"Bogomolov S, Forets M, Frehse G, Potomkin K, Schilling C. 2020. Reachability analysis of linear hybrid systems via block decomposition. Proceedings of the International Conference on Embedded Software. EMSOFT: Embedded Software.","ama":"Bogomolov S, Forets M, Frehse G, Potomkin K, Schilling C. Reachability analysis of linear hybrid systems via block decomposition. In: <i>Proceedings of the International Conference on Embedded Software</i>. ; 2020.","chicago":"Bogomolov, Sergiy, Marcelo Forets, Goran Frehse, Kostiantyn Potomkin, and Christian Schilling. “Reachability Analysis of Linear Hybrid Systems via Block Decomposition.” In <i>Proceedings of the International Conference on Embedded Software</i>, 2020."},"year":"2020","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","ddc":["000"],"date_published":"2020-10-01T00:00:00Z","file_date_updated":"2020-08-24T12:53:15Z","date_updated":"2026-04-03T09:32:00Z","publication":"Proceedings of the International Conference on Embedded Software","isi":1,"status":"public","ec_funded":1,"publication_status":"published","conference":{"location":"Virtual ","end_date":"2020-09-25","start_date":"2020-09-20","name":"EMSOFT: Embedded Software"},"file":[{"file_id":"8288","date_updated":"2020-08-24T12:53:15Z","creator":"cschilli","relation":"main_file","file_name":"2020EMSOFT.pdf","checksum":"d19e97d0f8a3a441dc078ec812297d75","file_size":696384,"date_created":"2020-08-24T12:53:15Z","success":1,"content_type":"application/pdf","access_level":"open_access"}],"arxiv":1,"keyword":["reachability","hybrid systems","decomposition"],"title":"Reachability analysis of linear hybrid systems via block decomposition","date_created":"2020-08-24T12:56:20Z","oa_version":"Preprint","oa":1,"author":[{"first_name":"Sergiy","last_name":"Bogomolov","full_name":"Bogomolov, Sergiy"},{"full_name":"Forets, Marcelo","last_name":"Forets","first_name":"Marcelo"},{"first_name":"Goran","last_name":"Frehse","full_name":"Frehse, Goran"},{"first_name":"Kostiantyn","last_name":"Potomkin","full_name":"Potomkin, Kostiantyn"},{"first_name":"Christian","id":"3A2F4DCE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3658-1065","full_name":"Schilling, Christian","last_name":"Schilling"}],"project":[{"grant_number":"S 11407_N23","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","name":"Rigorous Systems Engineering"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"}],"department":[{"_id":"ToHe"}],"month":"10","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"No","related_material":{"record":[{"id":"8790","status":"public","relation":"later_version"}]}}]