[{"publisher":"Elsevier","year":"2024","language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2023.12.002","type":"journal_article","_id":"14843","author":[{"id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","last_name":"Chen","first_name":"JingJing","full_name":"Chen, JingJing"},{"full_name":"Kaufmann, Walter","first_name":"Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann"},{"first_name":"Chong","full_name":"Chen, Chong","last_name":"Chen","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Arai","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","full_name":"Arai, Itaru","first_name":"Itaru"},{"full_name":"Kim, Olena","first_name":"Olena","last_name":"Kim","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi"},{"last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","first_name":"Peter M"}],"date_published":"2024-01-11T00:00:00Z","pmid":1,"acknowledgement":"We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C.","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"date_created":"2024-01-21T23:00:56Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","quality_controlled":"1","publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"month":"01","article_type":"original","date_updated":"2024-03-05T09:31:24Z","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"status":"public","ec_funded":1,"abstract":[{"text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.","lang":"eng"}],"oa_version":"None","publication_status":"inpress","day":"11","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020"},{"name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","call_identifier":"FWF"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232"},{"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"}],"citation":{"chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, n.d. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/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>. Elsevier.","ista":"Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron.","apa":"Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38; Jonas, P. M. (n.d.). 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>","short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron (n.d.).","mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, Elsevier, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">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>. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>"},"scopus_import":"1","external_id":{"pmid":["38215739"]},"related_material":{"link":[{"url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/","relation":"press_release","description":"News on ISTA Website"}]},"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","publication":"Neuron"},{"title":"Research data for the publication \"Imaging brain tissue architecture across millimeter to nanometer 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data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided via an external link due to the large size (>10GB) of the datasets. ","url":"https://pub.ista.ac.at/group_danzl/data/CATS/"}]},"has_accepted_license":"1","citation":{"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.","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>.","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>","short":"J.G. Danzl, (2023).","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>.","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>.","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>"},"project":[{"call_identifier":"FWF","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules"},{"call_identifier":"FWF","grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","call_identifier":"FWF","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":"715508","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"grant_number":"692692","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","grant_number":"101026635"}],"day":"04","tmp":{"image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","short":"CC BY-NC-SA (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"oa_version":"Published Version","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."}],"ec_funded":1,"status":"public","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","date_updated":"2024-02-21T12:18:19Z","month":"08","file_date_updated":"2023-08-04T13:19:47Z","ddc":["610"],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2023-06-07T07:15:12Z","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)","department":[{"_id":"JoDa"},{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"Bio"},{"_id":"RySh"}],"date_published":"2023-08-04T00:00:00Z","author":[{"orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","first_name":"Johann G"}],"_id":"13126","contributor":[{"last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","first_name":"Julia"},{"last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp"},{"last_name":"Stefanickova","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana"},{"first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","orcid":"0000-0002-8698-3823"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","orcid":"0000-0003-1216-9105"},{"first_name":"Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Roessler","first_name":"Karl"},{"first_name":"Thomas","last_name":"Czech"},{"last_name":"Höftberger","first_name":"Romana"},{"last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M"}],"oa":1,"type":"research_data","doi":"10.15479/AT:ISTA:13126","year":"2023","publisher":"Institute of Science and Technology Austria"},{"article_processing_charge":"Yes","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"        20","date_created":"2023-07-23T22:01:13Z","pmid":1,"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"}],"isi":1,"volume":20,"article_type":"original","month":"08","quality_controlled":"1","publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1038/s41592-023-01936-6","publisher":"Springer Nature","year":"2023","date_published":"2023-08-01T00:00:00Z","author":[{"first_name":"Philipp","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","orcid":"0000-0002-2340-7431"},{"full_name":"Miguel Villalba, Eder","first_name":"Eder","last_name":"Miguel Villalba","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5665-0430"},{"orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","full_name":"Michalska, Julia M","first_name":"Julia M"},{"full_name":"Lyudchik, Julia","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik"},{"first_name":"Donglai","full_name":"Wei, Donglai","last_name":"Wei"},{"last_name":"Lin","first_name":"Zudi","full_name":"Lin, Zudi"},{"orcid":"0000-0002-8698-3823","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","full_name":"Watson, Jake"},{"last_name":"Troidl","first_name":"Jakob","full_name":"Troidl, Jakob"},{"last_name":"Beyer","full_name":"Beyer, Johanna","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","first_name":"Yoav","full_name":"Ben Simon, Yoav"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"last_name":"Jahr","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","full_name":"Jahr, Wiebke"},{"first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"last_name":"Broichhagen","first_name":"Johannes","full_name":"Broichhagen, Johannes"},{"last_name":"Grant","full_name":"Grant, Seth G.N.","first_name":"Seth G.N."},{"full_name":"Jonas, Peter M","first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia"},{"last_name":"Pfister","full_name":"Pfister, Hanspeter","first_name":"Hanspeter"},{"last_name":"Bickel","id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","first_name":"Bernd"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G"}],"oa":1,"_id":"13267","scopus_import":"1","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF"},{"name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24"},{"grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385","call_identifier":"H2020"},{"name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","_id":"24F9549A-B435-11E9-9278-68D0E5697425","grant_number":"715767","call_identifier":"H2020"},{"call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"grant_number":"101026635","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057"}],"citation":{"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>","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.","ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>.","ieee":"P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023."},"publication":"Nature Methods","related_material":{"record":[{"status":"public","id":"12817","relation":"research_data"},{"relation":"shorter_version","id":"14770","status":"public"}],"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}]},"external_id":{"isi":["001025621500001"],"pmid":["37429995"]},"title":"Dense 4D nanoscale reconstruction of living brain tissue","main_file_link":[{"url":"https://doi.org/10.1038/s41592-023-01936-6","open_access":"1"}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"status":"public","date_updated":"2024-01-10T08:37:48Z","page":"1256-1265","publication_status":"published","oa_version":"Published Version","day":"01","ec_funded":1,"abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}]},{"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.).","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"date_created":"2023-09-03T22:01:15Z","article_processing_charge":"Yes (in subscription journal)","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"quality_controlled":"1","month":"08","article_type":"original","isi":1,"year":"2023","publisher":"Springer Nature","doi":"10.1038/s41587-023-01911-8","language":[{"iso":"eng"}],"type":"journal_article","_id":"14257","oa":1,"author":[{"first_name":"Julia M","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","orcid":"0000-0003-3862-1235"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","full_name":"Lyudchik, Julia","first_name":"Julia"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","orcid":"0000-0002-2340-7431","first_name":"Philipp","full_name":"Velicky, Philipp"},{"last_name":"Korinkova","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","full_name":"Korinkova, Hana"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","first_name":"Jake"},{"full_name":"Cenameri, Alban","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri"},{"orcid":"0000-0003-1216-9105","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"first_name":"Nicole","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg"},{"full_name":"Venturino, Alessandro","first_name":"Alessandro","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403"},{"last_name":"Roessler","full_name":"Roessler, Karl","first_name":"Karl"},{"last_name":"Czech","first_name":"Thomas","full_name":"Czech, Thomas"},{"full_name":"Höftberger, Romana","first_name":"Romana","last_name":"Höftberger"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","orcid":"0000-0001-8635-0877","first_name":"Sandra","full_name":"Siegert, Sandra"},{"full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","full_name":"Jonas, Peter M"},{"first_name":"Johann G","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl"}],"date_published":"2023-08-31T00:00:00Z","citation":{"ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2023. 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. (2023). 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>","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">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. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>. Springer Nature, 2023.","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, 2023. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>."},"project":[{"grant_number":"I03600","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24"},{"call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","grant_number":"715508"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385"},{"grant_number":"101026635","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41587-023-01911-8"}],"title":"Imaging brain tissue architecture across millimeter to nanometer scales","related_material":{"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}],"record":[{"relation":"research_data","status":"public","id":"13126"}]},"external_id":{"isi":["001065254200001"]},"publication":"Nature Biotechnology","date_updated":"2024-02-21T12:18:18Z","status":"public","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"ec_funded":1,"day":"31","publication_status":"epub_ahead","oa_version":"Published Version"},{"date_updated":"2023-08-01T13:46:39Z","status":"public","acknowledged_ssus":[{"_id":"EM-Fac"}],"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"}],"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"17","publication_status":"published","oa_version":"Published Version","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.","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>.","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>","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.","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>."},"project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"grant_number":"V00739","call_identifier":"FWF","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","name":"Structural plasticity at mossy fiber-CA3 synapses"}],"has_accepted_license":"1","scopus_import":"1","issue":"3 March","title":"Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy","file":[{"creator":"dernst","relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_size":7290413,"file_name":"2023_PLoSOne_Rothman.pdf","date_updated":"2023-03-27T06:51:09Z","success":1,"file_id":"12770","checksum":"2380331ec27cc87808826fc64419ac1c","date_created":"2023-03-27T06:51:09Z"}],"external_id":{"isi":["001024737400001"]},"publication":"PLoS ONE","year":"2023","publisher":"Public Library of Science","doi":"10.1371/journal.pone.0277148","language":[{"iso":"eng"}],"type":"journal_article","_id":"12759","oa":1,"author":[{"full_name":"Rothman, Jason Seth","first_name":"Jason Seth","last_name":"Rothman"},{"full_name":"Borges Merjane, Carolina","first_name":"Carolina","last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0005-401X"},{"full_name":"Holderith, Noemi","first_name":"Noemi","last_name":"Holderith"},{"last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","first_name":"Peter M"},{"last_name":"Angus Silver","full_name":"Angus Silver, R.","first_name":"R."}],"date_published":"2023-03-17T00:00:00Z","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).","department":[{"_id":"PeJo"}],"article_number":"e0277148","date_created":"2023-03-26T22:01:07Z","intvolume":"        18","file_date_updated":"2023-03-27T06:51:09Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"article_processing_charge":"No","publication_identifier":{"eissn":["1932-6203"]},"quality_controlled":"1","month":"03","volume":18,"article_type":"original","isi":1},{"date_updated":"2023-08-18T06:31:52Z","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"status":"public","degree_awarded":"PhD","ec_funded":1,"abstract":[{"lang":"eng","text":"One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.\r\n"}],"oa_version":"Published Version","publication_status":"published","page":"132","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"},"day":"20","project":[{"call_identifier":"H2020","grant_number":"708497","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020"},{"call_identifier":"FWF","grant_number":"W01205","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit"},{"call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize"}],"citation":{"ista":"Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria.","short":"O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022.","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>.","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>","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>","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>.","ieee":"O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022."},"alternative_title":["ISTA Thesis"],"has_accepted_license":"1","related_material":{"record":[{"relation":"part_of_dissertation","id":"11222","status":"public"},{"relation":"part_of_dissertation","id":"7473","status":"public"}]},"title":"Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses","file":[{"embargo":"2023-04-19","creator":"okim","access_level":"open_access","content_type":"application/pdf","relation":"main_file","file_name":"Olena_KIM_thesis_final.pdf","file_size":21273537,"file_id":"11220","date_created":"2022-04-20T14:21:56Z","checksum":"1616a8bf6f13a57c892dac873dcd0936","date_updated":"2023-04-20T22:30:03Z"},{"date_updated":"2023-04-20T22:30:03Z","embargo_to":"open_access","date_created":"2022-04-20T14:22:56Z","checksum":"1acb433f98dc42abb0b4b0cbb0c4b918","file_id":"11221","file_size":59248569,"file_name":"KIM_thesis_final.zip","content_type":"application/x-zip-compressed","relation":"source_file","access_level":"closed","creator":"okim"}],"publisher":"Institute of Science and Technology Austria","year":"2022","language":[{"iso":"eng"}],"doi":"10.15479/at:ista:11196","type":"dissertation","oa":1,"_id":"11196","author":[{"first_name":"Olena","full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","last_name":"Kim"}],"date_published":"2022-04-20T00:00:00Z","department":[{"_id":"PeJo"},{"_id":"GradSch"}],"date_created":"2022-04-20T09:47:12Z","ddc":["570"],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","file_date_updated":"2023-04-20T22:30:03Z","publication_identifier":{"issn":["2663-337X"]},"month":"04","supervisor":[{"first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804"}]},{"has_accepted_license":"1","citation":{"ama":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. <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.","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).","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>","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>."},"project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","call_identifier":"FWF"},{"call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"publication":"Nature Communications","file":[{"creator":"dernst","relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_size":5910357,"file_name":"2022_NatureCommunications_BenSimon.pdf","date_updated":"2022-08-26T11:51:40Z","success":1,"checksum":"405936d9e4d33625d80c093c9713a91f","file_id":"11990","date_created":"2022-08-26T11:51:40Z"}],"title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","external_id":{"isi":["000841396400008"]},"status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"date_updated":"2023-08-03T13:01:19Z","day":"16","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"oa_version":"Published Version","publication_status":"published","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"}],"ec_funded":1,"file_date_updated":"2022-08-26T11:51:40Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","ddc":["570"],"intvolume":"        13","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"article_number":"4826","date_created":"2022-08-24T08:25:50Z","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"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.).","isi":1,"volume":13,"article_type":"original","month":"08","publication_identifier":{"issn":["2041-1723"]},"quality_controlled":"1","type":"journal_article","doi":"10.1038/s41467-022-32559-8","language":[{"iso":"eng"}],"year":"2022","publisher":"Springer Nature","date_published":"2022-08-16T00:00:00Z","author":[{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","full_name":"Ben Simon, Yoav","first_name":"Yoav"},{"first_name":"Karola","full_name":"Käfer, Karola","last_name":"Käfer","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","first_name":"Philipp"},{"full_name":"Csicsvari, Jozsef L","first_name":"Jozsef L","orcid":"0000-0002-5193-4036","last_name":"Csicsvari","id":"3FA14672-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Danzl, Johann G","first_name":"Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","full_name":"Jonas, Peter M"}],"_id":"11951","oa":1},{"publication_status":"published","oa_version":"Published Version","day":"15","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"abstract":[{"text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.","lang":"eng"}],"date_updated":"2023-08-04T10:29:48Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"status":"public","publication":"eLife","external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","file":[{"file_name":"2022_eLife_Sumser.pdf","file_size":8506811,"date_created":"2023-01-30T11:50:53Z","file_id":"12463","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","date_updated":"2023-01-30T11:50:53Z","success":1,"creator":"dernst","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020"},{"grant_number":"756502","call_identifier":"H2020","name":"Circuits of Visual Attention","_id":"2634E9D2-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF"},{"name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425","grant_number":"LT000256"},{"_id":"264FEA02-B435-11E9-9278-68D0E5697425","name":"Connecting sensory with motor processing in the superior colliculus","grant_number":"ALTF 1098-2017"}],"citation":{"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>","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <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).","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>","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>.","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."},"scopus_import":"1","has_accepted_license":"1","author":[{"first_name":"Anton L","full_name":"Sumser, Anton L","orcid":"0000-0002-4792-1881","last_name":"Sumser","id":"3320A096-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Maximilian A","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","last_name":"Jösch"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","full_name":"Jonas, Peter M"},{"full_name":"Ben Simon, Yoav","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon"}],"oa":1,"_id":"12288","date_published":"2022-09-15T00:00:00Z","language":[{"iso":"eng"}],"doi":"10.7554/elife.79848","publisher":"eLife Sciences Publications","year":"2022","type":"journal_article","month":"09","quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"isi":1,"article_type":"original","volume":11,"date_created":"2023-01-16T10:04:15Z","article_number":"79848","pmid":1,"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).","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"file_date_updated":"2023-01-30T11:50:53Z","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"intvolume":"        11"},{"main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/647800","open_access":"1"}],"title":"How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network","file":[{"embargo":"2022-06-17","creator":"patrickd","relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_size":1699466,"file_name":"Guzmanetal2021.pdf","date_updated":"2022-06-18T22:30:03Z","date_created":"2022-06-02T12:51:07Z","checksum":"9fec5b667909ef52be96d502e4f8c2ae","file_id":"11430"},{"date_created":"2022-06-02T12:53:47Z","file_id":"11431","checksum":"52a005b13a114e3c3a28fa6bbe8b1a8d","date_updated":"2022-06-18T22:30:03Z","file_name":"Guzmanetal2021Suppl.pdf","file_size":3005651,"access_level":"open_access","relation":"supplementary_material","content_type":"application/pdf","embargo":"2022-06-17","creator":"patrickd","title":"Supplementary Material"}],"related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/spot-the-difference/"}],"record":[{"relation":"software","id":"10110","status":"public"}]},"publication":"Nature Computational Science","citation":{"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.","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>.","ama":"Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. <i>Nature Computational Science</i>. 2021;1(12):830-842. doi:<a href=\"https://doi.org/10.1038/s43588-021-00157-1\">10.1038/s43588-021-00157-1</a>","apa":"Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &#38; Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. <i>Nature Computational Science</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s43588-021-00157-1\">https://doi.org/10.1038/s43588-021-00157-1</a>","short":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, Nature Computational Science 1 (2021) 830–842.","ista":"Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. 1(12), 830–842.","mla":"Guzmán, José, et al. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” <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>."},"project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","call_identifier":"H2020"},{"grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize"}],"has_accepted_license":"1","scopus_import":"1","issue":"12","abstract":[{"text":"Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks.","lang":"eng"}],"ec_funded":1,"day":"16","oa_version":"Submitted Version","page":"830-842","publication_status":"published","date_updated":"2023-08-10T22:30:10Z","status":"public","acknowledged_ssus":[{"_id":"SSU"}],"publication_identifier":{"issn":["2662-8457"]},"quality_controlled":"1","month":"12","article_type":"original","volume":1,"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.).","date_created":"2022-03-04T08:32:36Z","intvolume":"         1","keyword":["general medicine"],"file_date_updated":"2022-06-18T22:30:03Z","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["610"],"_id":"10816","oa":1,"author":[{"first_name":"José","full_name":"Guzmán, José","orcid":"0000-0003-2209-5242","last_name":"Guzmán","id":"30CC5506-F248-11E8-B48F-1D18A9856A87"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","last_name":"Schlögl","orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois","first_name":"Alois"},{"first_name":"Claudia ","full_name":"Espinoza Martinez, Claudia ","orcid":"0000-0003-4710-2082","last_name":"Espinoza Martinez","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Zhang","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","full_name":"Zhang, Xiaomin"},{"id":"4952F31E-F248-11E8-B48F-1D18A9856A87","last_name":"Suter","orcid":"0000-0002-9885-6936","full_name":"Suter, Benjamin","first_name":"Benjamin"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","first_name":"Peter M"}],"date_published":"2021-12-16T00:00:00Z","year":"2021","publisher":"Springer Nature","doi":"10.1038/s43588-021-00157-1","language":[{"iso":"eng"}],"type":"journal_article"},{"month":"03","publication_identifier":{"eissn":["1872-678X"],"issn":["0165-0270"]},"quality_controlled":"1","isi":1,"volume":357,"article_type":"original","date_created":"2021-04-18T22:01:39Z","article_number":"109125","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"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.","file_date_updated":"2021-04-19T08:30:22Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"article_processing_charge":"Yes (via OA deal)","intvolume":"       357","author":[{"first_name":"Xiaomin","full_name":"Zhang, Xiaomin","last_name":"Zhang","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alois","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","last_name":"Schlögl"},{"last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","first_name":"David H","full_name":"Vandael, David H"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M"}],"_id":"9329","oa":1,"date_published":"2021-03-09T00:00:00Z","doi":"10.1016/j.jneumeth.2021.109125","language":[{"iso":"eng"}],"year":"2021","publisher":"Elsevier","type":"journal_article","publication":"Journal of Neuroscience Methods","file":[{"file_name":"2021_JourNeuroscienceMeth_Zhang.pdf","file_size":6924738,"date_created":"2021-04-19T08:30:22Z","checksum":"2a5800d91b96d08b525e17319dcd5e44","file_id":"9339","date_updated":"2021-04-19T08:30:22Z","success":1,"creator":"dernst","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","external_id":{"isi":["000661088500005"]},"citation":{"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.","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>.","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>","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.","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>","mla":"Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6, 109125, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">10.1016/j.jneumeth.2021.109125</a>.","short":"X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021)."},"project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"scopus_import":"1","issue":"6","has_accepted_license":"1","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"},"day":"09","oa_version":"Published Version","publication_status":"published","abstract":[{"text":"Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.\r\nNew method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.\r\nResults: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.\r\nComparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.\r\nConclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity.","lang":"eng"}],"ec_funded":1,"date_updated":"2023-08-07T14:36:14Z","status":"public","acknowledged_ssus":[{"_id":"SSU"}]},{"type":"conference","doi":"10.4230/LIPIcs.SoCG.2021.32","language":[{"iso":"eng"}],"year":"2021","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","date_published":"2021-06-02T00:00:00Z","author":[{"id":"3FB178DA-F248-11E8-B48F-1D18A9856A87","last_name":"Edelsbrunner","orcid":"0000-0002-9823-6833","full_name":"Edelsbrunner, Herbert","first_name":"Herbert"},{"id":"4879BB4E-F248-11E8-B48F-1D18A9856A87","last_name":"Heiss","orcid":"0000-0002-1780-2689","full_name":"Heiss, Teresa","first_name":"Teresa"},{"first_name":"Vitaliy","full_name":" Kurlin , Vitaliy","last_name":" Kurlin "},{"full_name":"Smith, Philip","first_name":"Philip","last_name":"Smith"},{"first_name":"Mathijs","full_name":"Wintraecken, Mathijs","orcid":"0000-0002-7472-2220","last_name":"Wintraecken","id":"307CFBC8-F248-11E8-B48F-1D18A9856A87"}],"_id":"9345","oa":1,"conference":{"name":"SoCG: Symposium on Computational Geometry","start_date":"2021-06-07","end_date":"2021-06-11","location":"Virtual"},"file_date_updated":"2021-04-22T08:08:14Z","ddc":["004","516"],"user_id":"D865714E-FA4E-11E9-B85B-F5C5E5697425","article_processing_charge":"No","intvolume":"       189","date_created":"2021-04-22T08:09:58Z","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.","department":[{"_id":"HeEd"}],"volume":189,"month":"06","publication_identifier":{"issn":["1868-8969"]},"quality_controlled":"1","status":"public","date_updated":"2023-02-23T13:55:40Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"02","publication_status":"published","oa_version":"Published Version","page":"32:1-32:16","abstract":[{"lang":"eng","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."}],"ec_funded":1,"has_accepted_license":"1","alternative_title":["LIPIcs"],"citation":{"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>.","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>.","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.","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>"},"project":[{"name":"Alpha Shape Theory Extended","_id":"266A2E9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"788183"},{"grant_number":"I4887","name":"Discretization in Geometry and Dynamics","_id":"0aa4bc98-070f-11eb-9043-e6fff9c6a316"},{"grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize"},{"call_identifier":"H2020","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships"}],"publication":"37th International Symposium on Computational Geometry (SoCG 2021)","title":"The density fingerprint of a periodic point set","file":[{"file_name":"df_socg_final_version.pdf","file_size":3117435,"file_id":"9346","checksum":"1787baef1523d6d93753b90d0c109a6d","date_created":"2021-04-22T08:08:14Z","success":1,"date_updated":"2021-04-22T08:08:14Z","creator":"mwintrae","access_level":"open_access","content_type":"application/pdf","relation":"main_file"}]},{"author":[{"full_name":"Vandael, David H","first_name":"David H","orcid":"0000-0001-7577-1676","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Okamoto, Yuji","first_name":"Yuji","id":"3337E116-F248-11E8-B48F-1D18A9856A87","last_name":"Okamoto","orcid":"0000-0003-0408-6094"},{"orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane","first_name":"Carolina","full_name":"Borges Merjane, Carolina"},{"first_name":"Victor M","full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","last_name":"Vargas Barroso"},{"last_name":"Suter","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9885-6936","first_name":"Benjamin","full_name":"Suter, Benjamin"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M"}],"_id":"9438","oa":1,"date_published":"2021-06-01T00:00:00Z","doi":"10.1038/s41596-021-00526-0","language":[{"iso":"eng"}],"year":"2021","publisher":"Springer Nature","type":"journal_article","month":"06","publication_identifier":{"issn":["17542189"],"eissn":["17502799"]},"quality_controlled":"1","isi":1,"volume":16,"article_type":"original","date_created":"2021-05-30T22:01:24Z","department":[{"_id":"PeJo"}],"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.","pmid":1,"file_date_updated":"2021-12-02T23:30:05Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","ddc":["570"],"intvolume":"        16","day":"01","page":"2947–2967","oa_version":"Submitted Version","publication_status":"published","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"}],"ec_funded":1,"date_updated":"2023-08-10T22:30:51Z","status":"public","acknowledged_ssus":[{"_id":"M-Shop"}],"publication":"Nature Protocols","title":"Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses","file":[{"file_id":"9639","date_created":"2021-07-08T12:27:55Z","checksum":"7eb580abd8893cdb0b410cf41bc8c263","date_updated":"2021-12-02T23:30:05Z","file_name":"VandaeletalAuthorVersion2021.pdf","file_size":38574802,"access_level":"open_access","content_type":"application/pdf","relation":"main_file","embargo":"2021-12-01","creator":"cziletti"}],"external_id":{"pmid":["33990799"],"isi":["000650528700003"]},"citation":{"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.","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>.","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.","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>","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>.","short":"D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967."},"project":[{"call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","grant_number":"V00739","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","name":"Structural plasticity at mossy fiber-CA3 synapses"}],"scopus_import":"1","issue":"6","has_accepted_license":"1"},{"publication":"Nature Communications","title":"Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses","file":[{"date_updated":"2021-12-17T11:34:50Z","success":1,"checksum":"6036a8cdae95e1707c2a04d54e325ff4","file_id":"10563","date_created":"2021-12-17T11:34:50Z","file_size":3108845,"file_name":"2021_NatureCommunications_Vandael.pdf","relation":"main_file","content_type":"application/pdf","access_level":"open_access","creator":"kschuh"}],"external_id":{"isi":["000655481800014"]},"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/"}]},"scopus_import":"1","issue":"1","has_accepted_license":"1","citation":{"mla":"Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” <i>Nature Communications</i>, vol. 12, no. 1, 2912, Springer, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23153-5\">10.1038/s41467-021-23153-5</a>.","apa":"Vandael, D. H., Okamoto, Y., &#38; Jonas, P. M. (2021). Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. <i>Nature Communications</i>. Springer. <a href=\"https://doi.org/10.1038/s41467-021-23153-5\">https://doi.org/10.1038/s41467-021-23153-5</a>","short":"D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021).","ista":"Vandael DH, Okamoto Y, Jonas PM. 2021. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. 12(1), 2912.","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>","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>.","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."},"project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"grant_number":"Z00312","call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"day":"18","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"oa_version":"Published Version","publication_status":"published","abstract":[{"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.","lang":"eng"}],"ec_funded":1,"status":"public","acknowledged_ssus":[{"_id":"SSU"}],"date_updated":"2023-08-10T14:16:16Z","isi":1,"article_type":"original","volume":12,"month":"05","publication_identifier":{"issn":["2041-1723"]},"quality_controlled":"1","file_date_updated":"2021-12-17T11:34:50Z","ddc":["570"],"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":"        12","keyword":["general physics and astronomy","general biochemistry","genetics and molecular biology","general chemistry"],"date_created":"2021-08-06T07:22:55Z","article_number":"2912","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.","department":[{"_id":"PeJo"}],"date_published":"2021-05-18T00:00:00Z","author":[{"full_name":"Vandael, David H","first_name":"David H","orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","last_name":"Vandael"},{"full_name":"Okamoto, Yuji","first_name":"Yuji","id":"3337E116-F248-11E8-B48F-1D18A9856A87","last_name":"Okamoto","orcid":"0000-0003-0408-6094"},{"first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804"}],"_id":"9778","oa":1,"type":"journal_article","doi":"10.1038/s41467-021-23153-5","language":[{"iso":"eng"}],"year":"2021","publisher":"Springer"},{"citation":{"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>","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>.","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.","short":"D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020) 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>.","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."},"project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","call_identifier":"H2020"},{"name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","call_identifier":"FWF"},{"_id":"2696E7FE-B435-11E9-9278-68D0E5697425","name":"Structural plasticity at mossy fiber-CA3 synapses","grant_number":"V00739","call_identifier":"FWF"}],"has_accepted_license":"1","scopus_import":"1","issue":"3","title":"Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation","file":[{"creator":"dernst","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_size":4390833,"file_name":"2020_Neuron_Vandael.pdf","success":1,"date_updated":"2020-11-25T11:23:02Z","file_id":"8811","date_created":"2020-11-25T11:23:02Z","checksum":"4030b2be0c9625d54694a1e9fb00305e"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/possible-physical-trace-of-short-term-memory-found/","description":"News on IST Homepage","relation":"press_release"}]},"external_id":{"pmid":["32492366"],"isi":["000556135600004"]},"publication":"Neuron","date_updated":"2023-08-22T07:45:25Z","status":"public","acknowledged_ssus":[{"_id":"SSU"}],"abstract":[{"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.","lang":"eng"}],"ec_funded":1,"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"},"day":"05","publication_status":"published","oa_version":"Published Version","page":"509-521","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.","department":[{"_id":"PeJo"}],"pmid":1,"date_created":"2020-06-22T13:29:05Z","intvolume":"       107","file_date_updated":"2020-11-25T11:23:02Z","article_processing_charge":"No","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_identifier":{"issn":["0896-6273"],"eissn":["10974199"]},"quality_controlled":"1","month":"08","article_type":"original","volume":107,"isi":1,"year":"2020","publisher":"Elsevier","doi":"10.1016/j.neuron.2020.05.013","language":[{"iso":"eng"}],"type":"journal_article","_id":"8001","oa":1,"author":[{"first_name":"David H","full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane","first_name":"Carolina","full_name":"Borges Merjane, Carolina"},{"id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","last_name":"Zhang","first_name":"Xiaomin","full_name":"Zhang, Xiaomin"},{"first_name":"Peter M","full_name":"Jonas, Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"}],"date_published":"2020-08-05T00:00:00Z"},{"day":"23","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"},"oa_version":"Published Version","page":"1212-1225","publication_status":"published","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."}],"ec_funded":1,"date_updated":"2023-08-22T08:30:55Z","status":"public","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"ScienComp"},{"_id":"PreCl"}],"publication":"Neuron","file":[{"relation":"main_file","content_type":"application/pdf","access_level":"open_access","creator":"dernst","date_updated":"2020-12-04T09:29:21Z","success":1,"checksum":"44a5960fc083a4cb3488d22224859fdc","date_created":"2020-12-04T09:29:21Z","file_id":"8920","file_size":3011120,"file_name":"2020_Neuron_Zhang.pdf"}],"title":"Selective routing of spatial information flow from input to output in hippocampal granule cells","related_material":{"link":[{"url":"https://ist.ac.at/en/news/the-bouncer-in-the-brain/","description":"News on IST Website","relation":"press_release"}]},"external_id":{"isi":["000579698700009"],"pmid":["32763145"]},"citation":{"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>","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>","short":"X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225.","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>.","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.","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.","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>."},"project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"issue":"6","has_accepted_license":"1","author":[{"last_name":"Zhang","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","full_name":"Zhang, Xiaomin"},{"orcid":"0000-0002-5621-8100","last_name":"Schlögl","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois","full_name":"Schlögl, Alois"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M"}],"_id":"8261","oa":1,"date_published":"2020-09-23T00:00:00Z","doi":"10.1016/j.neuron.2020.07.006","language":[{"iso":"eng"}],"year":"2020","publisher":"Elsevier","type":"journal_article","month":"09","publication_identifier":{"issn":["0896-6273"]},"quality_controlled":"1","isi":1,"article_type":"original","volume":107,"date_created":"2020-08-14T09:36:05Z","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"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.","pmid":1,"file_date_updated":"2020-12-04T09:29:21Z","ddc":["570"],"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":"       107"},{"year":"2020","language":[{"iso":"eng"}],"type":"conference","_id":"8287","oa":1,"author":[{"full_name":"Bogomolov, Sergiy","first_name":"Sergiy","last_name":"Bogomolov"},{"last_name":"Forets","first_name":"Marcelo","full_name":"Forets, Marcelo"},{"first_name":"Goran","full_name":"Frehse, Goran","last_name":"Frehse"},{"first_name":"Kostiantyn","full_name":"Potomkin, Kostiantyn","last_name":"Potomkin"},{"full_name":"Schilling, Christian","first_name":"Christian","orcid":"0000-0003-3658-1065","last_name":"Schilling","id":"3A2F4DCE-F248-11E8-B48F-1D18A9856A87"}],"date_published":"2020-01-01T00:00:00Z","department":[{"_id":"ToHe"}],"date_created":"2020-08-24T12:56:20Z","keyword":["reachability","hybrid systems","decomposition"],"conference":{"end_date":"2020-09-25","start_date":"2020-09-20","name":"EMSOFT: International Conference on Embedded Software","location":"Virtual "},"file_date_updated":"2020-08-24T12:53:15Z","ddc":["000"],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","quality_controlled":"1","date_updated":"2023-08-22T13:27:32Z","status":"public","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"}],"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication_status":"published","oa_version":"Preprint","arxiv":1,"citation":{"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.","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: International Conference on Embedded Software.","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 .","short":"S. Bogomolov, M. Forets, G. Frehse, K. Potomkin, C. Schilling, in:, Proceedings of the International Conference on Embedded Software, 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.","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.","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."},"project":[{"grant_number":"S 11407_N23","call_identifier":"FWF","name":"Rigorous Systems Engineering","_id":"25832EC2-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z00312"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"}],"has_accepted_license":"1","file":[{"date_updated":"2020-08-24T12:53:15Z","success":1,"date_created":"2020-08-24T12:53:15Z","checksum":"d19e97d0f8a3a441dc078ec812297d75","file_id":"8288","file_size":696384,"file_name":"2020EMSOFT.pdf","relation":"main_file","content_type":"application/pdf","access_level":"open_access","creator":"cschilli"}],"title":"Reachability analysis of linear hybrid systems via block decomposition","external_id":{"arxiv":["1905.02458"]},"related_material":{"record":[{"id":"8790","status":"public","relation":"later_version"}]},"publication":"Proceedings of the International Conference on Embedded Software"},{"citation":{"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.","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>.","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>","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.","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>.","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.","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>"},"project":[{"grant_number":"Z00312","call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"}],"title":"ARCH-COMP20 Category Report: Continuous and hybrid systems with linear dynamics","publication":"EPiC Series in Computing","main_file_link":[{"url":"https://easychair.org/publications/download/DRpS","open_access":"1"}],"status":"public","date_updated":"2021-01-12T08:20:06Z","abstract":[{"lang":"eng","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."}],"ec_funded":1,"day":"25","publication_status":"published","oa_version":"Published Version","page":"16-48","intvolume":"        74","conference":{"name":"ARCH: International Workshop on Applied Verification on Continuous and Hybrid Systems","end_date":"2020-07-12","start_date":"2020-07-12"},"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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.","department":[{"_id":"ToHe"}],"date_created":"2020-09-26T14:49:43Z","volume":74,"quality_controlled":"1","month":"09","type":"conference","year":"2020","publisher":"EasyChair","doi":"10.29007/7dt2","language":[{"iso":"eng"}],"date_published":"2020-09-25T00:00:00Z","_id":"8572","oa":1,"author":[{"last_name":"Althoff","first_name":"Matthias","full_name":"Althoff, Matthias"},{"first_name":"Stanley","full_name":"Bak, Stanley","last_name":"Bak"},{"last_name":"Bao","full_name":"Bao, Zongnan","first_name":"Zongnan"},{"full_name":"Forets, Marcelo","first_name":"Marcelo","last_name":"Forets"},{"first_name":"Goran","full_name":"Frehse, Goran","last_name":"Frehse"},{"last_name":"Freire","first_name":"Daniel","full_name":"Freire, Daniel"},{"full_name":"Kochdumper, Niklas","first_name":"Niklas","last_name":"Kochdumper"},{"first_name":"Yangge","full_name":"Li, Yangge","last_name":"Li"},{"first_name":"Sayan","full_name":"Mitra, Sayan","last_name":"Mitra"},{"last_name":"Ray","full_name":"Ray, Rajarshi","first_name":"Rajarshi"},{"last_name":"Schilling","id":"3A2F4DCE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3658-1065","first_name":"Christian","full_name":"Schilling, Christian"},{"last_name":"Schupp","first_name":"Stefan","full_name":"Schupp, Stefan"},{"full_name":"Wetzlinger, Mark","first_name":"Mark","last_name":"Wetzlinger"}]},{"article_processing_charge":"No","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file_date_updated":"2020-11-20T08:58:53Z","intvolume":"       105","date_created":"2020-02-10T15:59:45Z","pmid":1,"department":[{"_id":"PeJo"}],"acknowledgement":"This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie 708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27 Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa Zheden for extensive EM training, advice, and experimental assistance; Benjamin Suter for substantial help with light stimulation, ImageJ plugins for analysis, and manuscript editing; Florian Marr and Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing the Prox1-CreERT2 mouse line.","isi":1,"article_type":"original","volume":105,"month":"03","quality_controlled":"1","publication_identifier":{"issn":["0896-6273"]},"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2019.12.022","publisher":"Elsevier","year":"2020","date_published":"2020-03-18T00:00:00Z","author":[{"orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane","full_name":"Borges Merjane, Carolina","first_name":"Carolina"},{"id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","last_name":"Kim","full_name":"Kim, Olena","first_name":"Olena"},{"first_name":"Peter M","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"_id":"7473","scopus_import":"1","has_accepted_license":"1","project":[{"call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","call_identifier":"H2020","grant_number":"708497"},{"call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize"},{"_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205","call_identifier":"FWF"}],"citation":{"ieee":"C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” <i>Neuron</i>, vol. 105. Elsevier, pp. 992–1006, 2020.","chicago":"Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">https://doi.org/10.1016/j.neuron.2019.12.022</a>.","ama":"Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. <i>Neuron</i>. 2020;105:992-1006. doi:<a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">10.1016/j.neuron.2019.12.022</a>","mla":"Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” <i>Neuron</i>, vol. 105, Elsevier, 2020, pp. 992–1006, doi:<a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">10.1016/j.neuron.2019.12.022</a>.","short":"C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.","apa":"Borges Merjane, C., Kim, O., &#38; Jonas, P. M. (2020). Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">https://doi.org/10.1016/j.neuron.2019.12.022</a>","ista":"Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105, 992–1006."},"publication":"Neuron","external_id":{"isi":["000520854700008"],"pmid":["31928842"]},"related_material":{"link":[{"url":"https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/","description":"News on IST Homepage","relation":"press_release"}],"record":[{"relation":"dissertation_contains","id":"11196","status":"public"}]},"file":[{"access_level":"open_access","content_type":"application/pdf","relation":"main_file","creator":"dernst","file_id":"8778","checksum":"3582664addf26859e86ac5bec3e01416","date_created":"2020-11-20T08:58:53Z","success":1,"date_updated":"2020-11-20T08:58:53Z","file_name":"2020_Neuron_BorgesMerjane.pdf","file_size":9712957}],"title":"Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices","status":"public","date_updated":"2024-03-25T23:30:04Z","publication_status":"published","oa_version":"Published Version","page":"992-1006","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"},"day":"18","ec_funded":1,"abstract":[{"text":"How structural and functional properties of synapses relate to each other is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms of synaptic transmission, and electron microscopy (EM) has provided insight into morphological properties of synapses. Here we describe an enhanced method for functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure freezing. We demonstrate that the improved method can be applied to intact networks in acute brain slices and organotypic slice cultures from mice. As a proof of concept, we probed vesicle pool changes during synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked vesicle pool and the functionally defined readily releasable pool and provide evidence of fast endocytosis at this synapse. Functional EM with acute slices and slice cultures has the potential to reveal the structural and functional mechanisms of transmission in intact, genetically perturbed, and disease-affected synapses.","lang":"eng"}]},{"status":"public","date_updated":"2024-03-25T23:30:04Z","ec_funded":1,"day":"11","oa_version":"Published Version","publication_status":"published","issue":"Suppl. 1","citation":{"ama":"Kim O, Borges Merjane C, Jonas PM. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In: <i>Intrinsic Activity</i>. Vol 7. Austrian Pharmacological Society; 2019. doi:<a href=\"https://doi.org/10.25006/ia.7.s1-a3.27\">10.25006/ia.7.s1-a3.27</a>","apa":"Kim, O., Borges Merjane, C., &#38; Jonas, P. M. (2019). Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In <i>Intrinsic Activity</i> (Vol. 7). Innsbruck, Austria: Austrian Pharmacological Society. <a href=\"https://doi.org/10.25006/ia.7.s1-a3.27\">https://doi.org/10.25006/ia.7.s1-a3.27</a>","short":"O. Kim, C. Borges Merjane, P.M. Jonas, in:, Intrinsic Activity, Austrian Pharmacological Society, 2019.","ista":"Kim O, Borges Merjane C, Jonas PM. 2019. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. Intrinsic Activity. ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society vol. 7, A3.27.","mla":"Kim, Olena, et al. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” <i>Intrinsic Activity</i>, vol. 7, no. Suppl. 1, A3.27, Austrian Pharmacological Society, 2019, doi:<a href=\"https://doi.org/10.25006/ia.7.s1-a3.27\">10.25006/ia.7.s1-a3.27</a>.","ieee":"O. Kim, C. Borges Merjane, and P. M. Jonas, “Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy,” in <i>Intrinsic Activity</i>, Innsbruck, Austria, 2019, vol. 7, no. Suppl. 1.","chicago":"Kim, Olena, Carolina Borges Merjane, and Peter M Jonas. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” In <i>Intrinsic Activity</i>, Vol. 7. Austrian Pharmacological Society, 2019. <a href=\"https://doi.org/10.25006/ia.7.s1-a3.27\">https://doi.org/10.25006/ia.7.s1-a3.27</a>."},"project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"grant_number":"708497","call_identifier":"H2020","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse"},{"grant_number":"W01205","call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit"},{"grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize"}],"title":"Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy","related_material":{"record":[{"id":"11196","status":"public","relation":"dissertation_contains"}]},"publication":"Intrinsic Activity","main_file_link":[{"url":"https://www.intrinsicactivity.org/2019/7/S1/A3.27/","open_access":"1"}],"type":"conference_abstract","year":"2019","publisher":"Austrian Pharmacological Society","doi":"10.25006/ia.7.s1-a3.27","language":[{"iso":"eng"}],"date_published":"2019-09-11T00:00:00Z","_id":"11222","oa":1,"author":[{"id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","last_name":"Kim","first_name":"Olena","full_name":"Kim, Olena"},{"first_name":"Carolina","full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane"},{"first_name":"Peter M","full_name":"Jonas, Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"}],"intvolume":"         7","keyword":["hippocampus","mossy fibers","readily releasable pool","electron microscopy"],"conference":{"name":"ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society","start_date":"2019-09-25","end_date":"2019-09-27","location":"Innsbruck, Austria"},"article_processing_charge":"No","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","department":[{"_id":"PeJo"}],"acknowledgement":"This work was supported by the ERC and EU Horizon 2020 (ERC 692692; MSC-IF 708497) and FWF Z 312-B27 Wittgenstein award; W 1205-B09).","date_created":"2022-04-20T15:06:05Z","article_number":"A3.27","volume":7,"publication_identifier":{"issn":["2309-8503"]},"quality_controlled":"1","month":"09"},{"publication":"Neuron","external_id":{"isi":["000429192100016"]},"related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/a-certain-type-of-neurons-is-more-energy-efficient-than-previously-assumed/"}]},"file":[{"file_size":3180444,"file_name":"2018_Neuron_Hu.pdf","date_updated":"2020-07-14T12:46:03Z","file_id":"5690","date_created":"2018-12-17T10:37:50Z","checksum":"76070f3729f9c603e1080d0151aa2b11","creator":"dernst","relation":"main_file","content_type":"application/pdf","access_level":"open_access"}],"title":"Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons","project":[{"_id":"25C0F108-B435-11E9-9278-68D0E5697425","name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","grant_number":"268548","call_identifier":"FP7"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","call_identifier":"H2020"},{"call_identifier":"FWF","grant_number":"P24909-B24","name":"Mechanisms of transmitter release at GABAergic synapses","_id":"25C26B1E-B435-11E9-9278-68D0E5697425"},{"name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","call_identifier":"FWF"}],"citation":{"ieee":"H. Hu, F. Roth, D. H. Vandael, and P. M. Jonas, “Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons,” <i>Neuron</i>, vol. 98, no. 1. Elsevier, pp. 156–165, 2018.","chicago":"Hu, Hua, Fabian Roth, David H Vandael, and Peter M Jonas. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” <i>Neuron</i>. Elsevier, 2018. <a href=\"https://doi.org/10.1016/j.neuron.2018.02.024\">https://doi.org/10.1016/j.neuron.2018.02.024</a>.","ama":"Hu H, Roth F, Vandael DH, Jonas PM. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. <i>Neuron</i>. 2018;98(1):156-165. doi:<a href=\"https://doi.org/10.1016/j.neuron.2018.02.024\">10.1016/j.neuron.2018.02.024</a>","mla":"Hu, Hua, et al. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” <i>Neuron</i>, vol. 98, no. 1, Elsevier, 2018, pp. 156–65, doi:<a href=\"https://doi.org/10.1016/j.neuron.2018.02.024\">10.1016/j.neuron.2018.02.024</a>.","ista":"Hu H, Roth F, Vandael DH, Jonas PM. 2018. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. 98(1), 156–165.","apa":"Hu, H., Roth, F., Vandael, D. H., &#38; Jonas, P. M. (2018). Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2018.02.024\">https://doi.org/10.1016/j.neuron.2018.02.024</a>","short":"H. Hu, F. Roth, D.H. Vandael, P.M. Jonas, Neuron 98 (2018) 156–165."},"issue":"1","scopus_import":"1","has_accepted_license":"1","page":"156 - 165","oa_version":"Published Version","publication_status":"published","day":"04","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"abstract":[{"lang":"eng","text":"Fast-spiking, parvalbumin-expressing GABAergic interneurons (PV+-BCs) express a complex machinery of rapid signaling mechanisms, including specialized voltage-gated ion channels to generate brief action potentials (APs). However, short APs are associated with overlapping Na+ and K+ fluxes and are therefore energetically expensive. How the potentially vicious combination of high AP frequency and inefficient spike generation can be reconciled with limited energy supply is presently unclear. To address this question, we performed direct recordings from the PV+-BC axon, the subcellular structure where active conductances for AP initiation and propagation are located. Surprisingly, the energy required for the AP was, on average, only ∼1.6 times the theoretical minimum. High energy efficiency emerged from the combination of fast inactivation of Na+ channels and delayed activation of Kv3-type K+ channels, which minimized ion flux overlap during APs. Thus, the complementary tuning of axonal Na+ and K+ channel gating optimizes both fast signaling properties and metabolic efficiency. Hu et al. demonstrate that action potentials in parvalbumin-expressing GABAergic interneuron axons are energetically efficient, which is highly unexpected given their brief duration. High energy efficiency emerges from the combination of fast inactivation of voltage-gated Na+ channels and delayed activation of Kv3 channels in the axon. "}],"date_updated":"2023-09-11T12:45:10Z","status":"public","month":"04","quality_controlled":"1","publist_id":"7545","isi":1,"volume":98,"date_created":"2018-12-11T11:45:48Z","department":[{"_id":"PeJo"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"article_processing_charge":"Yes (in subscription journal)","file_date_updated":"2020-07-14T12:46:03Z","intvolume":"        98","author":[{"full_name":"Hu, Hua","first_name":"Hua","last_name":"Hu","id":"4AC0145C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Roth, Fabian","first_name":"Fabian","last_name":"Roth"},{"last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H","first_name":"David H"},{"full_name":"Jonas, Peter M","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas"}],"oa":1,"_id":"320","date_published":"2018-04-04T00:00:00Z","language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2018.02.024","publisher":"Elsevier","year":"2018","type":"journal_article"}]