[{"related_material":{"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/"}]},"year":"2024","doi":"10.1016/j.neuron.2023.12.002","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"ec_funded":1,"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","external_id":{"pmid":["38215739"]},"article_processing_charge":"No","date_updated":"2024-03-05T09:31:24Z","publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"_id":"14843","pmid":1,"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","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232"},{"_id":"26B66A3E-B435-11E9-9278-68D0E5697425","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","grant_number":"25383"}],"quality_controlled":"1","oa_version":"None","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.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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>.","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>","ieee":"J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” <i>Neuron</i>. Elsevier.","short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron (n.d.).","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.","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>"},"publication_status":"inpress","abstract":[{"lang":"eng","text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission."}],"author":[{"id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","last_name":"Chen","full_name":"Chen, JingJing","first_name":"JingJing"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","last_name":"Kaufmann","first_name":"Walter"},{"id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, Chong","last_name":"Chen","first_name":"Chong"},{"id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","first_name":"Itaru","full_name":"Arai, Itaru","last_name":"Arai"},{"full_name":"Kim, Olena","last_name":"Kim","first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ryuichi","full_name":"Shigemoto, 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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>","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>","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>.","short":"J.G. Danzl, (2023)."},"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."}],"author":[{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973"}],"oa":1,"date_updated":"2024-02-21T12:18:19Z","article_processing_charge":"No","_id":"13126","acknowledgement":"We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr, Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger, Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for support with obtaining human samples. We gratefully acknowledge Eder Miguel for setting up webKnossos and Marek Šuplata for computational support and hardware control. We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing, imaging and optics, preclinical, and lab support facilities, and by the Library and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources: \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual Fellowship 101026635 under the EU Horizon 2020 program (JFW)","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"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","call_identifier":"FWF"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","call_identifier":"FWF"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"grant_number":"715508","_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"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"year":"2023","doi":"10.15479/AT:ISTA:13126","ec_funded":1,"title":"Research data for the publication \"Imaging brain tissue architecture across millimeter to nanometer scales\"","contributor":[{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","first_name":"Julia M"},{"last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-2340-7431","last_name":"Velicky","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","last_name":"Stefanickova"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","last_name":"Watson","orcid":"0000-0002-8698-3823"},{"first_name":"Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-3183-8207","last_name":"Amberg","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","orcid":"0000-0003-2356-9403","first_name":"Alessandro"},{"last_name":"Roessler","first_name":"Karl"},{"last_name":"Czech","first_name":"Thomas"},{"first_name":"Romana","last_name":"Höftberger"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","orcid":"0000-0001-8635-0877","last_name":"Siegert"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804"}],"tmp":{"short":"CC BY-NC-SA (4.0)","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"related_material":{"link":[{"url":"https://pub.ista.ac.at/group_danzl/data/CATS/","description":"Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided via an external link due to the large size (>10GB) of the datasets. ","relation":"research_data"}],"record":[{"id":"14257","relation":"used_in_publication","status":"public"}]},"ddc":["610"]},{"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"date_created":"2023-07-23T22:01:13Z","date_published":"2023-08-01T00:00:00Z","article_type":"original","month":"08","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Springer Nature","page":"1256-1265","publication":"Nature Methods","type":"journal_article","day":"01","status":"public","intvolume":"        20","isi":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41592-023-01936-6"}],"related_material":{"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}],"record":[{"relation":"research_data","id":"12817","status":"public"},{"relation":"shorter_version","id":"14770","status":"public"}]},"ec_funded":1,"year":"2023","doi":"10.1038/s41592-023-01936-6","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"title":"Dense 4D nanoscale reconstruction of living brain tissue","article_processing_charge":"Yes","volume":20,"date_updated":"2024-01-10T08:37:48Z","oa":1,"quality_controlled":"1","project":[{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"},{"grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385"},{"grant_number":"715767","call_identifier":"H2020","_id":"24F9549A-B435-11E9-9278-68D0E5697425","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling"},{"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","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"grant_number":"101026635","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057"}],"oa_version":"Published Version","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.).","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"_id":"13267","pmid":1,"citation":{"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>","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>.","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.","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.","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>","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>."},"publication_status":"published","author":[{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp"},{"orcid":"0000-0001-5665-0430","last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder","first_name":"Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia M","last_name":"Michalska","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia"},{"first_name":"Donglai","full_name":"Wei, Donglai","last_name":"Wei"},{"last_name":"Lin","full_name":"Lin, Zudi","first_name":"Zudi"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson","first_name":"Jake"},{"last_name":"Troidl","full_name":"Troidl, Jakob","first_name":"Jakob"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","last_name":"Jahr","full_name":"Jahr, Wiebke"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","full_name":"Cenameri, Alban","first_name":"Alban"},{"full_name":"Broichhagen, Johannes","last_name":"Broichhagen","first_name":"Johannes"},{"last_name":"Grant","full_name":"Grant, Seth G.N.","first_name":"Seth G.N."},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","first_name":"Bernd","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","last_name":"Bickel"},{"first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue.","lang":"eng"}]},{"isi":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41587-023-01911-8"}],"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}],"record":[{"status":"public","relation":"research_data","id":"13126"}]},"ec_funded":1,"year":"2023","doi":"10.1038/s41587-023-01911-8","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"external_id":{"isi":["001065254200001"]},"title":"Imaging brain tissue architecture across millimeter to nanometer scales","article_processing_charge":"Yes (in subscription journal)","oa":1,"date_updated":"2024-02-21T12:18:18Z","quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"},{"call_identifier":"FWF","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"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"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020"},{"grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020"}],"oa_version":"Published Version","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.).","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"_id":"14257","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>","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).","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>","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>."},"publication_status":"epub_ahead","author":[{"first_name":"Julia M","last_name":"Michalska","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","last_name":"Velicky"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova","full_name":"Korinkova, Hana","first_name":"Hana"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","full_name":"Watson, Jake","last_name":"Watson","orcid":"0000-0002-8698-3823"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","full_name":"Cenameri, Alban","first_name":"Alban"},{"first_name":"Christoph M","full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","last_name":"Amberg","first_name":"Nicole"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","first_name":"Alessandro"},{"full_name":"Roessler, Karl","last_name":"Roessler","first_name":"Karl"},{"last_name":"Czech","full_name":"Czech, Thomas","first_name":"Thomas"},{"last_name":"Höftberger","full_name":"Höftberger, Romana","first_name":"Romana"},{"full_name":"Siegert, Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"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."}],"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"date_created":"2023-09-03T22:01:15Z","date_published":"2023-08-31T00:00:00Z","article_type":"original","month":"08","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Springer Nature","publication":"Nature Biotechnology","type":"journal_article","day":"31","status":"public"},{"doi":"10.3389/fnana.2022.1097467","year":"2023","external_id":{"pmid":["36704406"],"isi":["000919786900001"]},"title":"The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway","article_number":"1097467","isi":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"publication_status":"published","citation":{"apa":"Ortiz-Leal, I., Torres, M. V., Vargas Barroso, V. M., Fidalgo, L. E., López-Beceiro, A. M., Larriva-Sahd, J. A., &#38; Sánchez-Quinteiro, P. (2023). The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. <i>Frontiers in Neuroanatomy</i>. Frontiers. <a href=\"https://doi.org/10.3389/fnana.2022.1097467\">https://doi.org/10.3389/fnana.2022.1097467</a>","ieee":"I. Ortiz-Leal <i>et al.</i>, “The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway,” <i>Frontiers in Neuroanatomy</i>, vol. 16. Frontiers, 2023.","chicago":"Ortiz-Leal, Irene, Mateo V. Torres, Victor M Vargas Barroso, Luis Eusebio Fidalgo, Ana María López-Beceiro, Jorge A. Larriva-Sahd, and Pablo Sánchez-Quinteiro. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” <i>Frontiers in Neuroanatomy</i>. Frontiers, 2023. <a href=\"https://doi.org/10.3389/fnana.2022.1097467\">https://doi.org/10.3389/fnana.2022.1097467</a>.","mla":"Ortiz-Leal, Irene, et al. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” <i>Frontiers in Neuroanatomy</i>, vol. 16, 1097467, Frontiers, 2023, doi:<a href=\"https://doi.org/10.3389/fnana.2022.1097467\">10.3389/fnana.2022.1097467</a>.","ama":"Ortiz-Leal I, Torres MV, Vargas Barroso VM, et al. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. <i>Frontiers in Neuroanatomy</i>. 2023;16. doi:<a href=\"https://doi.org/10.3389/fnana.2022.1097467\">10.3389/fnana.2022.1097467</a>","ista":"Ortiz-Leal I, Torres MV, Vargas Barroso VM, Fidalgo LE, López-Beceiro AM, Larriva-Sahd JA, Sánchez-Quinteiro P. 2023. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. 16, 1097467.","short":"I. Ortiz-Leal, M.V. Torres, V.M. Vargas Barroso, L.E. Fidalgo, A.M. López-Beceiro, J.A. Larriva-Sahd, P. Sánchez-Quinteiro, Frontiers in Neuroanatomy 16 (2023)."},"author":[{"last_name":"Ortiz-Leal","full_name":"Ortiz-Leal, Irene","first_name":"Irene"},{"first_name":"Mateo V.","last_name":"Torres","full_name":"Torres, Mateo V."},{"id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","full_name":"Vargas Barroso, Victor M","last_name":"Vargas Barroso","first_name":"Victor M"},{"first_name":"Luis Eusebio","last_name":"Fidalgo","full_name":"Fidalgo, Luis Eusebio"},{"first_name":"Ana María","full_name":"López-Beceiro, Ana María","last_name":"López-Beceiro"},{"last_name":"Larriva-Sahd","full_name":"Larriva-Sahd, Jorge A.","first_name":"Jorge A."},{"full_name":"Sánchez-Quinteiro, Pablo","last_name":"Sánchez-Quinteiro","first_name":"Pablo"}],"abstract":[{"text":"Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents.\r\nMethods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques.\r\nResults: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity.\r\nDiscussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues.","lang":"eng"}],"date_updated":"2023-08-16T11:37:52Z","volume":16,"oa":1,"article_processing_charge":"No","acknowledgement":"This work was partially supported by a grant from “Consello Social Universidade de Santiago de Compostela” 2022-PU004.We would like to show special gratitude to Prof. Ludwig Wagner (Medical University, Vienna) for kindly providing us with the secretagogin antibody. We thank the Wildlife Recovery Centres of Galicia, Dirección Xeral de Patrimonio Natural (Xunta de Galicia, Spain), and Federación Galega de Caza for providing the red foxes used in this study.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","oa_version":"Published Version","_id":"12515","pmid":1,"publication_identifier":{"eissn":["1662-5129"]},"article_type":"original","date_published":"2023-01-10T00:00:00Z","month":"01","language":[{"iso":"eng"}],"publisher":"Frontiers","scopus_import":"1","department":[{"_id":"PeJo"}],"has_accepted_license":"1","date_created":"2023-02-05T23:01:00Z","file":[{"date_updated":"2023-02-06T07:56:14Z","access_level":"open_access","file_name":"2022_FrontiersNeuroanatomy_OrtizLeal.pdf","file_size":21943473,"date_created":"2023-02-06T07:56:14Z","checksum":"49cd40f3bda6f267079427042e7d15e3","content_type":"application/pdf","relation":"main_file","creator":"dernst","file_id":"12518","success":1}],"type":"journal_article","day":"10","status":"public","intvolume":"        16","file_date_updated":"2023-02-06T07:56:14Z","publication":"Frontiers in Neuroanatomy"},{"file_date_updated":"2023-02-20T07:09:27Z","issue":"3","publication":"International Journal of Molecular Sciences","type":"journal_article","day":"21","status":"public","intvolume":"        24","department":[{"_id":"PeJo"}],"has_accepted_license":"1","file":[{"success":1,"file_id":"12569","creator":"dernst","relation":"main_file","content_type":"application/pdf","checksum":"69a35dcd3e0249f902ab881b06ee2e58","date_created":"2023-02-20T07:09:27Z","file_size":2823025,"file_name":"2023_IJMS_Mrestani.pdf","access_level":"open_access","date_updated":"2023-02-20T07:09:27Z"}],"date_created":"2023-02-19T23:00:56Z","article_type":"original","date_published":"2023-01-21T00:00:00Z","month":"01","language":[{"iso":"eng"}],"publisher":"MDPI","scopus_import":"1","oa":1,"date_updated":"2023-08-01T13:16:36Z","volume":24,"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"This work has been supported by funding of the German Research Foundation (Deutsche Forschungsgemeinschaft [DFG], CRC 166, Project B06 to M.H. and A.-L.S., FOR 3004 SYNABS P1 to M.H.) and by the Interdisciplinary Clinical Research Center (IZKF) Würzburg (Z-3/69 to M.M.P., N-229 to M.H. and A.-L.S.). A.M. is funded by the University of Leipzig Clinician Scientist Program.","quality_controlled":"1","oa_version":"Published Version","_id":"12567","publication_identifier":{"eissn":["1422-0067"]},"publication_status":"published","citation":{"chicago":"Mrestani, Achmed, Katharina Lichter, Anna Leena Sirén, Manfred Heckmann, Mila M. Paul, and Martin Pauli. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” <i>International Journal of Molecular Sciences</i>. MDPI, 2023. <a href=\"https://doi.org/10.3390/ijms24032128\">https://doi.org/10.3390/ijms24032128</a>.","ieee":"A. Mrestani, K. Lichter, A. L. Sirén, M. Heckmann, M. M. Paul, and M. Pauli, “Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation,” <i>International Journal of Molecular Sciences</i>, vol. 24, no. 3. MDPI, 2023.","apa":"Mrestani, A., Lichter, K., Sirén, A. L., Heckmann, M., Paul, M. M., &#38; Pauli, M. (2023). Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. <i>International Journal of Molecular Sciences</i>. MDPI. <a href=\"https://doi.org/10.3390/ijms24032128\">https://doi.org/10.3390/ijms24032128</a>","short":"A. Mrestani, K. Lichter, A.L. Sirén, M. Heckmann, M.M. Paul, M. Pauli, International Journal of Molecular Sciences 24 (2023).","ista":"Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. 2023. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. 24(3), 2128.","ama":"Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. <i>International Journal of Molecular Sciences</i>. 2023;24(3). doi:<a href=\"https://doi.org/10.3390/ijms24032128\">10.3390/ijms24032128</a>","mla":"Mrestani, Achmed, et al. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” <i>International Journal of Molecular Sciences</i>, vol. 24, no. 3, 2128, MDPI, 2023, doi:<a href=\"https://doi.org/10.3390/ijms24032128\">10.3390/ijms24032128</a>."},"author":[{"first_name":"Achmed","full_name":"Mrestani, Achmed","last_name":"Mrestani"},{"id":"39302e62-fcfc-11ec-8196-8b01447dbd3d","first_name":"Katharina","last_name":"Lichter","full_name":"Lichter, Katharina"},{"first_name":"Anna Leena","full_name":"Sirén, Anna Leena","last_name":"Sirén"},{"first_name":"Manfred","full_name":"Heckmann, Manfred","last_name":"Heckmann"},{"first_name":"Mila M.","last_name":"Paul","full_name":"Paul, Mila M."},{"last_name":"Pauli","full_name":"Pauli, Martin","first_name":"Martin"}],"abstract":[{"lang":"eng","text":"Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations."}],"isi":1,"article_number":"2128","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"doi":"10.3390/ijms24032128","year":"2023","external_id":{"isi":["000930324700001"]},"title":"Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation"},{"language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Springer Nature","date_published":"2023-03-01T00:00:00Z","month":"03","date_created":"2023-03-12T23:01:02Z","department":[{"_id":"PeJo"}],"status":"public","intvolume":"      2633","series_title":"MIMB","type":"book_chapter","day":"01","page":"33-44","publication":"DNA Manipulation and Analysis","title":"Molecular Cloning Using In Vivo DNA Assembly","external_id":{"pmid":["36853454"]},"year":"2023","doi":"10.1007/978-1-0716-3004-4_3","place":"New York, NY, United States","alternative_title":["Methods in Molecular Biology"],"author":[{"first_name":"Sandra","full_name":"Arroyo-Urea, Sandra","last_name":"Arroyo-Urea"},{"full_name":"Watson, Jake","last_name":"Watson","orcid":"0000-0002-8698-3823","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"last_name":"García-Nafría","full_name":"García-Nafría, Javier","first_name":"Javier"}],"abstract":[{"lang":"eng","text":"Here we describe the in vivo DNA assembly approach, where molecular cloning procedures are performed using an E. coli recA-independent recombination pathway, which assembles linear fragments of DNA with short homologous termini. This pathway is present in all standard laboratory E. coli strains and, by bypassing the need for in vitro DNA assembly, allows simplified molecular cloning to be performed without the plasmid instability issues associated with specialized recombination-cloning bacterial strains. The methodology requires specific primer design and can perform all standard plasmid modifications (insertions, deletions, mutagenesis, and sub-cloning) in a rapid, simple, and cost-efficient manner, as it does not require commercial kits or specialized bacterial strains. Additionally, this approach can be used to perform complex procedures such as multiple modifications to a plasmid, as up to 6 linear fragments can be assembled in vivo by this recombination pathway. Procedures generally require less than 3 h, involving PCR amplification, DpnI digestion of template DNA, and transformation, upon which circular plasmids are assembled. In this chapter we describe the requirements, procedure, and potential pitfalls when using this technique, as well as protocol variations to overcome the most common issues."}],"citation":{"short":"S. Arroyo-Urea, J. Watson, J. García-Nafría, in:, G. Scarlett (Ed.), DNA Manipulation and Analysis, Springer Nature, New York, NY, United States, 2023, pp. 33–44.","ista":"Arroyo-Urea S, Watson J, García-Nafría J. 2023.Molecular Cloning Using In Vivo DNA Assembly. In: DNA Manipulation and Analysis. Methods in Molecular Biology, vol. 2633, 33–44.","ama":"Arroyo-Urea S, Watson J, García-Nafría J. Molecular Cloning Using In Vivo DNA Assembly. In: Scarlett G, ed. <i>DNA Manipulation and Analysis</i>. Vol 2633. MIMB. New York, NY, United States: Springer Nature; 2023:33-44. doi:<a href=\"https://doi.org/10.1007/978-1-0716-3004-4_3\">10.1007/978-1-0716-3004-4_3</a>","mla":"Arroyo-Urea, Sandra, et al. “Molecular Cloning Using In Vivo DNA Assembly.” <i>DNA Manipulation and Analysis</i>, edited by Garry Scarlett, vol. 2633, Springer Nature, 2023, pp. 33–44, doi:<a href=\"https://doi.org/10.1007/978-1-0716-3004-4_3\">10.1007/978-1-0716-3004-4_3</a>.","chicago":"Arroyo-Urea, Sandra, Jake Watson, and Javier García-Nafría. “Molecular Cloning Using In Vivo DNA Assembly.” In <i>DNA Manipulation and Analysis</i>, edited by Garry Scarlett, 2633:33–44. MIMB. New York, NY, United States: Springer Nature, 2023. <a href=\"https://doi.org/10.1007/978-1-0716-3004-4_3\">https://doi.org/10.1007/978-1-0716-3004-4_3</a>.","ieee":"S. Arroyo-Urea, J. Watson, and J. García-Nafría, “Molecular Cloning Using In Vivo DNA Assembly,” in <i>DNA Manipulation and Analysis</i>, vol. 2633, G. Scarlett, Ed. New York, NY, United States: Springer Nature, 2023, pp. 33–44.","apa":"Arroyo-Urea, S., Watson, J., &#38; García-Nafría, J. (2023). Molecular Cloning Using In Vivo DNA Assembly. In G. Scarlett (Ed.), <i>DNA Manipulation and Analysis</i> (Vol. 2633, pp. 33–44). New York, NY, United States: Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-3004-4_3\">https://doi.org/10.1007/978-1-0716-3004-4_3</a>"},"publication_status":"published","quality_controlled":"1","oa_version":"None","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["1064-3745"],"isbn":["978-1-0716-3003-7"],"eisbn":["978-1-0716-3004-4"],"eissn":["1940-6029"]},"pmid":1,"_id":"12720","article_processing_charge":"No","volume":2633,"date_updated":"2023-03-16T08:34:24Z","editor":[{"first_name":"Garry","last_name":"Scarlett","full_name":"Scarlett, Garry"}]},{"external_id":{"isi":["001024737400001"]},"title":"Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy","ec_funded":1,"year":"2023","doi":"10.1371/journal.pone.0277148","acknowledged_ssus":[{"_id":"EM-Fac"}],"ddc":["570"],"isi":1,"article_number":"e0277148","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"author":[{"first_name":"Jason Seth","last_name":"Rothman","full_name":"Rothman, Jason Seth"},{"first_name":"Carolina","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Holderith, Noemi","last_name":"Holderith","first_name":"Noemi"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M"},{"first_name":"R.","full_name":"Angus Silver, R.","last_name":"Angus Silver"}],"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"}],"citation":{"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.","short":"J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver, PLoS ONE 18 (2023).","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>","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>.","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>.","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>","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."},"publication_status":"published","project":[{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z00312"},{"name":"Structural plasticity at mossy fiber-CA3 synapses","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"V00739"}],"oa_version":"Published Version","quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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).","publication_identifier":{"eissn":["1932-6203"]},"_id":"12759","article_processing_charge":"No","oa":1,"date_updated":"2023-08-01T13:46:39Z","volume":18,"language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Public Library of Science","article_type":"original","date_published":"2023-03-17T00:00:00Z","month":"03","date_created":"2023-03-26T22:01:07Z","file":[{"content_type":"application/pdf","relation":"main_file","file_id":"12770","creator":"dernst","success":1,"date_updated":"2023-03-27T06:51:09Z","access_level":"open_access","file_name":"2023_PLoSOne_Rothman.pdf","file_size":7290413,"date_created":"2023-03-27T06:51:09Z","checksum":"2380331ec27cc87808826fc64419ac1c"}],"department":[{"_id":"PeJo"}],"has_accepted_license":"1","status":"public","intvolume":"        18","type":"journal_article","day":"17","file_date_updated":"2023-03-27T06:51:09Z","publication":"PLoS ONE","issue":"3 March"},{"author":[{"last_name":"Zhang","full_name":"Zhang, Danyang","first_name":"Danyang"},{"first_name":"Remigijus","last_name":"Lape","full_name":"Lape, Remigijus"},{"last_name":"Shaikh","full_name":"Shaikh, Saher A.","first_name":"Saher A."},{"full_name":"Kohegyi, Bianka K.","last_name":"Kohegyi","first_name":"Bianka K."},{"first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Ondrej","last_name":"Cais","full_name":"Cais, Ondrej"},{"first_name":"Terunaga","full_name":"Nakagawa, Terunaga","last_name":"Nakagawa"},{"full_name":"Greger, Ingo H.","last_name":"Greger","first_name":"Ingo H."}],"abstract":[{"lang":"eng","text":"AMPA glutamate receptors (AMPARs) mediate excitatory neurotransmission throughout the brain. Their signalling is uniquely diversified by brain region-specific auxiliary subunits, providing an opportunity for the development of selective therapeutics. AMPARs associated with TARP γ8 are enriched in the hippocampus, and are targets of emerging anti-epileptic drugs. To understand their therapeutic activity, we determined cryo-EM structures of the GluA1/2-γ8 receptor associated with three potent, chemically diverse ligands. We find that despite sharing a lipid-exposed and water-accessible binding pocket, drug action is differentially affected by binding-site mutants. Together with patch-clamp recordings and MD simulations we also demonstrate that ligand-triggered reorganisation of the AMPAR-TARP interface contributes to modulation. Unexpectedly, one ligand (JNJ-61432059) acts bifunctionally, negatively affecting GluA1 but exerting positive modulatory action on GluA2-containing AMPARs, in a TARP stoichiometry-dependent manner. These results further illuminate the action of TARPs, demonstrate the sensitive balance between positive and negative modulatory action, and provide a mechanistic platform for development of both positive and negative selective AMPAR modulators."}],"citation":{"ama":"Zhang D, Lape R, Shaikh SA, et al. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. <i>Nature Communications</i>. 2023;14. doi:<a href=\"https://doi.org/10.1038/s41467-023-37259-5\">10.1038/s41467-023-37259-5</a>","mla":"Zhang, Danyang, et al. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor Therapeutics.” <i>Nature Communications</i>, vol. 14, 1659, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41467-023-37259-5\">10.1038/s41467-023-37259-5</a>.","ista":"Zhang D, Lape R, Shaikh SA, Kohegyi BK, Watson J, Cais O, Nakagawa T, Greger IH. 2023. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. 14, 1659.","short":"D. Zhang, R. Lape, S.A. Shaikh, B.K. Kohegyi, J. Watson, O. Cais, T. Nakagawa, I.H. Greger, Nature Communications 14 (2023).","ieee":"D. Zhang <i>et al.</i>, “Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics,” <i>Nature Communications</i>, vol. 14. Springer Nature, 2023.","apa":"Zhang, D., Lape, R., Shaikh, S. A., Kohegyi, B. K., Watson, J., Cais, O., … Greger, I. H. (2023). Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-023-37259-5\">https://doi.org/10.1038/s41467-023-37259-5</a>","chicago":"Zhang, Danyang, Remigijus Lape, Saher A. Shaikh, Bianka K. Kohegyi, Jake Watson, Ondrej Cais, Terunaga Nakagawa, and Ingo H. Greger. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor Therapeutics.” <i>Nature Communications</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41467-023-37259-5\">https://doi.org/10.1038/s41467-023-37259-5</a>."},"publication_status":"published","oa_version":"Published Version","quality_controlled":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"We thank James Krieger for generating the ‘proDy’ interaction maps in Fig. 5B and S7C, and Jan-Niklas Dohrke for critically reading the manuscript. We thank members of the Greger lab for insightful comments during this study. We acknowledge Trevor Rutherford for confirming ligand integrity by NMR. We are also grateful to LMB scientific computing and the EM facility for their support. This research was funded in part by the Wellcome Trust (223194/Z/21/Z) to I.H.G. For the purpose of Open Access, the MRC Laboratory of Molecular Biology has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission. Further funding came from the Medical Research Council (MRU105174197) to I.H.G, and NIH grant (R56/R01MH123474) to T.N.","publication_identifier":{"eissn":["2041-1723"]},"_id":"12786","article_processing_charge":"No","date_updated":"2023-12-13T11:15:58Z","volume":14,"oa":1,"title":"Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics","external_id":{"isi":["001066658700003"]},"year":"2023","doi":"10.1038/s41467-023-37259-5","ddc":["570"],"isi":1,"article_number":"1659","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","intvolume":"        14","type":"journal_article","day":"25","file_date_updated":"2023-04-03T06:38:56Z","publication":"Nature Communications","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Springer Nature","date_published":"2023-03-25T00:00:00Z","article_type":"original","month":"03","file":[{"file_size":2613996,"file_name":"2023_NatureComm_Zhang.pdf","checksum":"0a97b31191432dae5853bbb5ccb7698d","date_created":"2023-04-03T06:38:56Z","access_level":"open_access","date_updated":"2023-04-03T06:38:56Z","success":1,"relation":"main_file","content_type":"application/pdf","file_id":"12797","creator":"dernst"}],"date_created":"2023-04-02T22:01:09Z","department":[{"_id":"PeJo"}],"has_accepted_license":"1"},{"doi":"10.1038/s41467-022-28404-7","year":"2022","external_id":{"isi":["000757297200008"],"pmid":["35136046"]},"title":"Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"734","isi":1,"ddc":["570"],"citation":{"ista":"Herguedas B, Kohegyi BK, Dohrke JN, Watson J, Zhang D, Ho H, Shaikh SA, Lape R, Krieger JM, Greger IH. 2022. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 13, 734.","short":"B. Herguedas, B.K. Kohegyi, J.N. Dohrke, J. Watson, D. Zhang, H. Ho, S.A. Shaikh, R. Lape, J.M. Krieger, I.H. Greger, Nature Communications 13 (2022).","mla":"Herguedas, Beatriz, et al. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” <i>Nature Communications</i>, vol. 13, 734, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-28404-7\">10.1038/s41467-022-28404-7</a>.","ama":"Herguedas B, Kohegyi BK, Dohrke JN, et al. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-28404-7\">10.1038/s41467-022-28404-7</a>","chicago":"Herguedas, Beatriz, Bianka K. Kohegyi, Jan Niklas Dohrke, Jake Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, and Ingo H. Greger. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-28404-7\">https://doi.org/10.1038/s41467-022-28404-7</a>.","apa":"Herguedas, B., Kohegyi, B. K., Dohrke, J. N., Watson, J., Zhang, D., Ho, H., … Greger, I. H. (2022). Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-28404-7\">https://doi.org/10.1038/s41467-022-28404-7</a>","ieee":"B. Herguedas <i>et al.</i>, “Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022."},"publication_status":"published","abstract":[{"lang":"eng","text":"AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory\r\nsynapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs)\r\nleads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission\r\nand are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs)\r\nthrough currently incompletely resolved mechanisms. Here, electron cryo-microscopy\r\nstructures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states\r\n(at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’),\r\nelucidating how this TARP stabilizes specific gating states. We further show how TARPs alter\r\nchannel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we\r\nreveal that the Q/R-editing site couples the channel constriction at the filter entrance to the\r\ngate, and forms the major cation binding site in the conduction path. Our results provide a\r\nmechanistic framework of how TARPs modulate AMPAR gating and conductance."}],"author":[{"first_name":"Beatriz","full_name":"Herguedas, Beatriz","last_name":"Herguedas"},{"full_name":"Kohegyi, Bianka K.","last_name":"Kohegyi","first_name":"Bianka K."},{"first_name":"Jan Niklas","last_name":"Dohrke","full_name":"Dohrke, Jan Niklas"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson"},{"last_name":"Zhang","full_name":"Zhang, Danyang","first_name":"Danyang"},{"full_name":"Ho, Hinze","last_name":"Ho","first_name":"Hinze"},{"first_name":"Saher A.","full_name":"Shaikh, Saher A.","last_name":"Shaikh"},{"full_name":"Lape, Remigijus","last_name":"Lape","first_name":"Remigijus"},{"first_name":"James M.","last_name":"Krieger","full_name":"Krieger, James M."},{"first_name":"Ingo H.","last_name":"Greger","full_name":"Greger, Ingo H."}],"article_processing_charge":"No","oa":1,"date_updated":"2023-08-02T14:25:33Z","volume":13,"publication_identifier":{"eissn":["20411723"]},"_id":"10763","pmid":1,"oa_version":"Published Version","quality_controlled":"1","acknowledgement":"We thank Ondrej Cais for critical reading of the manuscript. We are grateful to LMB\r\nscientific computing and the EM facility for support, Paul Emsley for help with model\r\nbuilding and Takanori Nakane for helpful comments with Relion 3.1. This work was\r\nsupported by grants from the Medical Research Council (MC_U105174197) and BBSRC\r\n(BB/N002113/1) to I.H.G, and grants from the MCIN/AEI/ 10.13039/501100011033 and\r\n“ESF Investing in your future” to B.H (PID2019-106284GA-I00 and RYC2018-025720-I).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"02","article_type":"original","date_published":"2022-02-08T00:00:00Z","scopus_import":"1","publisher":"Springer Nature","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"PeJo"}],"date_created":"2022-02-20T23:01:30Z","file":[{"checksum":"d86ee8eabe8b794730729ffbb1a8832e","date_created":"2022-02-21T07:59:32Z","file_size":2625540,"file_name":"2022_NatureCommunications_Herguedas.pdf","access_level":"open_access","date_updated":"2022-02-21T07:59:32Z","success":1,"creator":"dernst","file_id":"10778","relation":"main_file","content_type":"application/pdf"}],"day":"08","type":"journal_article","intvolume":"        13","status":"public","publication":"Nature Communications","file_date_updated":"2022-02-21T07:59:32Z"},{"author":[{"first_name":"Olena","full_name":"Kim, Olena","last_name":"Kim","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"}],"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"}],"citation":{"chicago":"Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11196\">https://doi.org/10.15479/at:ista:11196</a>.","ieee":"O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022.","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>","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>.","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>"},"publication_status":"published","project":[{"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":"708497"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"W01205","call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","call_identifier":"FWF"}],"oa_version":"Published Version","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","publication_identifier":{"issn":["2663-337X"]},"_id":"11196","article_processing_charge":"No","date_updated":"2023-08-18T06:31:52Z","oa":1,"title":"Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses","ec_funded":1,"year":"2022","doi":"10.15479/at:ista:11196","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"ddc":["570"],"related_material":{"record":[{"relation":"part_of_dissertation","id":"11222","status":"public"},{"status":"public","id":"7473","relation":"part_of_dissertation"}]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"alternative_title":["ISTA Thesis"],"status":"public","supervisor":[{"first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"type":"dissertation","day":"20","page":"132","file_date_updated":"2023-04-20T22:30:03Z","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","date_published":"2022-04-20T00:00:00Z","month":"04","file":[{"relation":"main_file","content_type":"application/pdf","creator":"okim","file_id":"11220","access_level":"open_access","date_updated":"2023-04-20T22:30:03Z","file_size":21273537,"embargo":"2023-04-19","file_name":"Olena_KIM_thesis_final.pdf","checksum":"1616a8bf6f13a57c892dac873dcd0936","date_created":"2022-04-20T14:21:56Z"},{"embargo_to":"open_access","access_level":"closed","date_updated":"2023-04-20T22:30:03Z","file_size":59248569,"file_name":"KIM_thesis_final.zip","checksum":"1acb433f98dc42abb0b4b0cbb0c4b918","date_created":"2022-04-20T14:22:56Z","relation":"source_file","content_type":"application/x-zip-compressed","file_id":"11221","creator":"okim"}],"date_created":"2022-04-20T09:47:12Z","department":[{"_id":"PeJo"},{"_id":"GradSch"}],"has_accepted_license":"1","degree_awarded":"PhD"},{"abstract":[{"lang":"eng","text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full <jats:italic>in-silico</jats:italic> reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches<jats:sup>6–12</jats:sup> facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy<jats:sup>6,13</jats:sup> in extracellularly labelled tissue<jats:sup>14</jats:sup> for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue."}],"author":[{"first_name":"Philipp","orcid":"0000-0002-2340-7431","last_name":"Velicky","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder","orcid":"0000-0001-5665-0430","first_name":"Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Michalska","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Wei","full_name":"Wei, Donglai","first_name":"Donglai"},{"first_name":"Zudi","full_name":"Lin, Zudi","last_name":"Lin"},{"first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Jakob","last_name":"Troidl","full_name":"Troidl, Jakob"},{"last_name":"Beyer","full_name":"Beyer, Johanna","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","full_name":"Ben Simon, Yoav","first_name":"Yoav"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105"},{"first_name":"Wiebke","last_name":"Jahr","full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"full_name":"Grant, Seth G. N.","last_name":"Grant","first_name":"Seth G. N."},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","first_name":"Bernd","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","last_name":"Bickel"},{"orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"status":"public","day":"09","citation":{"chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>.","ieee":"P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>","ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, <a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>"},"publication_status":"submitted","type":"preprint","_id":"11943","oa_version":"Preprint","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"bioRxiv","article_processing_charge":"No","date_updated":"2024-03-25T23:30:11Z","oa":1,"title":"Saturated reconstruction of living brain tissue","publisher":"Cold Spring Harbor Laboratory","language":[{"iso":"eng"}],"doi":"10.1101/2022.03.16.484431","year":"2022","month":"05","date_published":"2022-05-09T00:00:00Z","related_material":{"record":[{"id":"12470","relation":"dissertation_contains","status":"public"}]},"date_created":"2022-08-23T11:07:59Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.03.16.484431"}],"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}]},{"status":"public","author":[{"first_name":"Julia M","last_name":"Michalska","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Philipp","orcid":"0000-0002-2340-7431","last_name":"Velicky","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Korinkova","full_name":"Korinkova, Hana","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"first_name":"Jake","full_name":"Watson, Jake","last_name":"Watson","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"first_name":"Alessandro","full_name":"Venturino, Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Roessler, Karl","last_name":"Roessler","first_name":"Karl"},{"first_name":"Thomas","full_name":"Czech, Thomas","last_name":"Czech"},{"first_name":"Sandra","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"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 nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons.","lang":"eng"}],"type":"preprint","day":"18","citation":{"apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.)."},"publication_status":"submitted","oa_version":"Preprint","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"11950","article_processing_charge":"No","date_updated":"2024-03-25T23:30:11Z","oa":1,"publication":"bioRxiv","language":[{"iso":"eng"}],"title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","publisher":"Cold Spring Harbor Laboratory","date_published":"2022-08-18T00:00:00Z","doi":"10.1101/2022.08.17.504272","year":"2022","month":"08","date_created":"2022-08-24T08:24:52Z","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12470"}]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}],"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}]},{"ec_funded":1,"year":"2022","doi":"10.1038/s41467-022-32559-8","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"external_id":{"isi":["000841396400008"]},"title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","article_number":"4826","isi":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"citation":{"mla":"Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” <i>Nature Communications</i>, vol. 13, 4826, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32559-8\">10.1038/s41467-022-32559-8</a>.","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.","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>."},"publication_status":"published","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"author":[{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","full_name":"Ben Simon, Yoav","first_name":"Yoav"},{"id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","full_name":"Käfer, Karola","last_name":"Käfer","first_name":"Karola"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","last_name":"Velicky","first_name":"Philipp"},{"orcid":"0000-0002-5193-4036","last_name":"Csicsvari","full_name":"Csicsvari, Jozsef L","first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"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"}],"article_processing_charge":"No","volume":13,"oa":1,"date_updated":"2023-08-03T13:01:19Z","quality_controlled":"1","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312"}],"oa_version":"Published Version","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.).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_identifier":{"issn":["2041-1723"]},"_id":"11951","date_published":"2022-08-16T00:00:00Z","article_type":"original","month":"08","language":[{"iso":"eng"}],"publisher":"Springer Nature","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"has_accepted_license":"1","date_created":"2022-08-24T08:25:50Z","file":[{"success":1,"creator":"dernst","file_id":"11990","content_type":"application/pdf","relation":"main_file","date_created":"2022-08-26T11:51:40Z","checksum":"405936d9e4d33625d80c093c9713a91f","file_name":"2022_NatureCommunications_BenSimon.pdf","file_size":5910357,"date_updated":"2022-08-26T11:51:40Z","access_level":"open_access"}],"type":"journal_article","day":"16","status":"public","intvolume":"        13","file_date_updated":"2022-08-26T11:51:40Z","publication":"Nature Communications"},{"intvolume":"        11","status":"public","day":"15","type":"journal_article","publication":"eLife","file_date_updated":"2023-01-30T11:50:53Z","publisher":"eLife Sciences Publications","scopus_import":"1","language":[{"iso":"eng"}],"month":"09","article_type":"original","date_published":"2022-09-15T00:00:00Z","file":[{"creator":"dernst","file_id":"12463","content_type":"application/pdf","relation":"main_file","success":1,"date_updated":"2023-01-30T11:50:53Z","access_level":"open_access","date_created":"2023-01-30T11:50:53Z","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","file_name":"2022_eLife_Sumser.pdf","file_size":8506811}],"date_created":"2023-01-16T10:04:15Z","has_accepted_license":"1","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"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"}],"author":[{"last_name":"Sumser","full_name":"Sumser, Anton L","orcid":"0000-0002-4792-1881","first_name":"Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Maximilian A","last_name":"Jösch","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","full_name":"Ben Simon, Yoav","last_name":"Ben Simon"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"publication_status":"published","citation":{"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>.","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","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.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","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>"},"pmid":1,"_id":"12288","publication_identifier":{"eissn":["2050-084X"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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).","project":[{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"grant_number":"756502","call_identifier":"H2020","name":"Circuits of Visual Attention","_id":"2634E9D2-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"grant_number":"ALTF 1098-2017","_id":"264FEA02-B435-11E9-9278-68D0E5697425","name":"Connecting sensory with motor processing in the superior colliculus"}],"quality_controlled":"1","oa_version":"Published Version","oa":1,"date_updated":"2023-08-04T10:29:48Z","volume":11,"article_processing_charge":"No","external_id":{"pmid":["36040301"],"isi":["000892204300001"]},"title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"doi":"10.7554/elife.79848","year":"2022","ec_funded":1,"ddc":["570"],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"79848","isi":1},{"intvolume":"         1","status":"public","day":"16","type":"journal_article","publication":"Nature Computational Science","issue":"12","page":"830-842","file_date_updated":"2022-06-18T22:30:03Z","scopus_import":"1","publisher":"Springer Nature","language":[{"iso":"eng"}],"month":"12","date_published":"2021-12-16T00:00:00Z","article_type":"original","date_created":"2022-03-04T08:32:36Z","file":[{"file_name":"Guzmanetal2021.pdf","embargo":"2022-06-17","file_size":1699466,"date_created":"2022-06-02T12:51:07Z","checksum":"9fec5b667909ef52be96d502e4f8c2ae","date_updated":"2022-06-18T22:30:03Z","access_level":"open_access","content_type":"application/pdf","relation":"main_file","creator":"patrickd","file_id":"11430"},{"date_updated":"2022-06-18T22:30:03Z","access_level":"open_access","date_created":"2022-06-02T12:53:47Z","checksum":"52a005b13a114e3c3a28fa6bbe8b1a8d","file_name":"Guzmanetal2021Suppl.pdf","embargo":"2022-06-17","file_size":3005651,"creator":"patrickd","file_id":"11431","content_type":"application/pdf","relation":"supplementary_material","title":"Supplementary Material"}],"has_accepted_license":"1","department":[{"_id":"PeJo"}],"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"}],"author":[{"orcid":"0000-0003-2209-5242","full_name":"Guzmán, José","last_name":"Guzmán","first_name":"José","id":"30CC5506-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alois","last_name":"Schlögl","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Claudia ","orcid":"0000-0003-4710-2082","full_name":"Espinoza Martinez, Claudia ","last_name":"Espinoza Martinez","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Zhang, Xiaomin","last_name":"Zhang","first_name":"Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87"},{"id":"4952F31E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9885-6936","last_name":"Suter","full_name":"Suter, Benjamin","first_name":"Benjamin"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"}],"keyword":["general medicine"],"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.","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>","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>","mla":"Guzmán, José, et al. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” <i>Nature Computational Science</i>, vol. 1, no. 12, Springer Nature, 2021, pp. 830–42, doi:<a href=\"https://doi.org/10.1038/s43588-021-00157-1\">10.1038/s43588-021-00157-1</a>.","short":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, Nature Computational Science 1 (2021) 830–842.","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."},"publication_status":"published","publication_identifier":{"issn":["2662-8457"]},"_id":"10816","quality_controlled":"1","oa_version":"Submitted Version","project":[{"call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z00312"}],"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.).","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","oa":1,"date_updated":"2023-08-10T22:30:10Z","volume":1,"title":"How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network","doi":"10.1038/s43588-021-00157-1","year":"2021","acknowledged_ssus":[{"_id":"SSU"}],"ec_funded":1,"related_material":{"record":[{"status":"public","relation":"software","id":"10110"}],"link":[{"url":"https://ista.ac.at/en/news/spot-the-difference/","relation":"press_release"}]},"ddc":["610"],"main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/647800"}]},{"article_type":"original","date_published":"2021-01-26T00:00:00Z","month":"01","language":[{"iso":"eng"}],"publisher":"Springer Nature","scopus_import":"1","department":[{"_id":"PeJo"}],"has_accepted_license":"1","date_created":"2021-02-07T23:01:12Z","file":[{"relation":"main_file","content_type":"application/pdf","file_id":"9106","creator":"dernst","success":1,"access_level":"open_access","date_updated":"2021-02-09T07:33:23Z","file_size":2885056,"file_name":"2021_ScientificReports_Pandey.pdf","checksum":"e8a68df48750712671f5c47b0228e531","date_created":"2021-02-09T07:33:23Z"}],"type":"journal_article","day":"26","status":"public","intvolume":"        11","file_date_updated":"2021-02-09T07:33:23Z","publication":"Scientific Reports","doi":"10.1038/s41598-020-80507-7","year":"2021","title":"Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis","article_number":"2204","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"publication_status":"published","citation":{"mla":"Pandey, Rakesh, et al. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” <i>Scientific Reports</i>, vol. 11, 2204, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41598-020-80507-7\">10.1038/s41598-020-80507-7</a>.","ama":"Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. <i>Scientific Reports</i>. 2021;11. doi:<a href=\"https://doi.org/10.1038/s41598-020-80507-7\">10.1038/s41598-020-80507-7</a>","short":"R. Pandey, Y. Al-Nuaimi, R.K. Mishra, S.K. Spurgeon, M. Goodfellow, Scientific Reports 11 (2021).","ista":"Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. 2021. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 11, 2204.","apa":"Pandey, R., Al-Nuaimi, Y., Mishra, R. K., Spurgeon, S. K., &#38; Goodfellow, M. (2021). Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. <i>Scientific Reports</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41598-020-80507-7\">https://doi.org/10.1038/s41598-020-80507-7</a>","ieee":"R. Pandey, Y. Al-Nuaimi, R. K. Mishra, S. K. Spurgeon, and M. Goodfellow, “Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis,” <i>Scientific Reports</i>, vol. 11. Springer Nature, 2021.","chicago":"Pandey, Rakesh, Yusur Al-Nuaimi, Rajiv Kumar Mishra, Sarah K. Spurgeon, and Marc Goodfellow. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” <i>Scientific Reports</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41598-020-80507-7\">https://doi.org/10.1038/s41598-020-80507-7</a>."},"author":[{"first_name":"Rakesh","full_name":"Pandey, Rakesh","last_name":"Pandey"},{"first_name":"Yusur","last_name":"Al-Nuaimi","full_name":"Al-Nuaimi, Yusur"},{"last_name":"Mishra","full_name":"Mishra, Rajiv Kumar","first_name":"Rajiv Kumar","id":"46CB58F2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sarah K.","full_name":"Spurgeon, Sarah K.","last_name":"Spurgeon"},{"first_name":"Marc","last_name":"Goodfellow","full_name":"Goodfellow, Marc"}],"abstract":[{"lang":"eng","text":"Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving TNFα, IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of TNFα, IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of TNFα would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis."}],"date_updated":"2022-08-19T07:22:23Z","volume":11,"oa":1,"article_processing_charge":"No","acknowledgement":"RP acknowledges the Department of Science and Technology, India for the support through the DST-INSPIRE Faculty Award (DST/INSPIRE/04/2015/001939). This work was supported by the Engineering and Physical Sciences Research Council (EPSRC), United Kingdom (Grant numbers EP/J018295/1, EP/J018392/1, EP/N014391/1). The contribution of RP was also supported by the later Grant. This work was generously supported by the Welcome Trust Institutional Strategic Support Award (204909/Z/16/Z) too. The contribution of MG was supported by the EPSRC via EP/N014391/1 and a Wellcome Trust Institutional Strategic Support Award (WT105618MA). The contribution of YA was generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA).","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","oa_version":"Published Version","_id":"9097","publication_identifier":{"eissn":["20452322"]}},{"status":"public","intvolume":"       357","type":"journal_article","day":"09","file_date_updated":"2021-04-19T08:30:22Z","publication":"Journal of Neuroscience Methods","issue":"6","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Elsevier","date_published":"2021-03-09T00:00:00Z","article_type":"original","month":"03","date_created":"2021-04-18T22:01:39Z","file":[{"access_level":"open_access","date_updated":"2021-04-19T08:30:22Z","checksum":"2a5800d91b96d08b525e17319dcd5e44","date_created":"2021-04-19T08:30:22Z","file_size":6924738,"file_name":"2021_JourNeuroscienceMeth_Zhang.pdf","file_id":"9339","creator":"dernst","relation":"main_file","content_type":"application/pdf","success":1}],"department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"has_accepted_license":"1","author":[{"first_name":"Xiaomin","full_name":"Zhang, Xiaomin","last_name":"Zhang","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","last_name":"Schlögl","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","first_name":"Alois"},{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","last_name":"Vandael","full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","first_name":"David H"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804"}],"abstract":[{"lang":"eng","text":"Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.\r\nNew method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.\r\nResults: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.\r\nComparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.\r\nConclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity."}],"citation":{"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>.","apa":"Zhang, X., Schlögl, A., Vandael, D. H., &#38; Jonas, P. M. (2021). MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. <i>Journal of Neuroscience Methods</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">https://doi.org/10.1016/j.jneumeth.2021.109125</a>","ieee":"X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo,” <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6. Elsevier, 2021.","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.","short":"X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021).","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>","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>."},"publication_status":"published","project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z00312"}],"quality_controlled":"1","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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.","publication_identifier":{"eissn":["1872-678X"],"issn":["0165-0270"]},"_id":"9329","article_processing_charge":"Yes (via OA deal)","volume":357,"date_updated":"2023-08-07T14:36:14Z","oa":1,"external_id":{"isi":["000661088500005"]},"title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","ec_funded":1,"year":"2021","doi":"10.1016/j.jneumeth.2021.109125","acknowledged_ssus":[{"_id":"SSU"}],"ddc":["570"],"article_number":"109125","isi":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"}},{"language":[{"iso":"eng"}],"scopus_import":"1","publisher":"eLife Sciences Publications","article_type":"original","date_published":"2021-04-29T00:00:00Z","month":"04","file":[{"success":1,"relation":"main_file","content_type":"application/pdf","file_id":"9440","creator":"cziletti","file_size":8174719,"file_name":"2021_eLife_Bhandari.pdf","checksum":"6ebcb79999f889766f7cd79ee134ad28","date_created":"2021-05-31T09:43:09Z","access_level":"open_access","date_updated":"2021-05-31T09:43:09Z"}],"date_created":"2021-05-30T22:01:23Z","department":[{"_id":"RySh"},{"_id":"PeJo"}],"has_accepted_license":"1","status":"public","intvolume":"        10","type":"journal_article","day":"29","file_date_updated":"2021-05-31T09:43:09Z","publication":"eLife","title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","external_id":{"isi":["000651761700001"]},"ec_funded":1,"year":"2021","doi":"10.7554/ELIFE.68274","ddc":["570"],"related_material":{"record":[{"relation":"dissertation_contains","id":"9562","status":"public"}],"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.04.16.045112"}]},"isi":1,"article_number":"e68274","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"author":[{"id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","full_name":"Bhandari, Pradeep","last_name":"Bhandari","orcid":"0000-0003-0863-4481","first_name":"Pradeep"},{"orcid":"0000-0001-7577-1676","last_name":"Vandael","full_name":"Vandael, David H","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Diego","last_name":"Fernández-Fernández","full_name":"Fernández-Fernández, Diego"},{"first_name":"Thorsten","last_name":"Fritzius","full_name":"Fritzius, Thorsten"},{"first_name":"David","last_name":"Kleindienst","full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"id":"4659D740-F248-11E8-B48F-1D18A9856A87","full_name":"Önal, Hüseyin C","last_name":"Önal","orcid":"0000-0002-2771-2011","first_name":"Hüseyin C"},{"first_name":"Jacqueline-Claire","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","last_name":"Montanaro-Punzengruber","id":"3786AB44-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gassmann, Martin","last_name":"Gassmann","first_name":"Martin"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kulik, Akos","last_name":"Kulik","first_name":"Akos"},{"first_name":"Bernhard","full_name":"Bettler, Bernhard","last_name":"Bettler"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","first_name":"Peter"}],"abstract":[{"lang":"eng","text":"The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation."}],"citation":{"short":"P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, H.C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).","ista":"Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal HC, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B, Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274.","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>.","chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>.","apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>","ieee":"P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021."},"publication_status":"published","oa_version":"Published Version","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020","grant_number":"694539"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385"}],"quality_controlled":"1","acknowledgement":"We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_identifier":{"eissn":["2050-084X"]},"_id":"9437","article_processing_charge":"No","volume":10,"date_updated":"2024-03-25T23:30:16Z","oa":1},{"doi":"10.1038/s41596-021-00526-0","year":"2021","acknowledged_ssus":[{"_id":"M-Shop"}],"ec_funded":1,"external_id":{"isi":["000650528700003"],"pmid":["33990799"]},"title":"Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses","isi":1,"ddc":["570"],"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.","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>","chicago":"Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” <i>Nature Protocols</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>.","mla":"Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” <i>Nature Protocols</i>, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967, doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>.","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.","short":"D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967."},"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"}],"author":[{"orcid":"0000-0001-7577-1676","last_name":"Vandael","full_name":"Vandael, David H","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"id":"3337E116-F248-11E8-B48F-1D18A9856A87","first_name":"Yuji","orcid":"0000-0003-0408-6094","last_name":"Okamoto","full_name":"Okamoto, Yuji"},{"id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina","orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane"},{"first_name":"Victor M","last_name":"Vargas Barroso","full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-9885-6936","full_name":"Suter, Benjamin","last_name":"Suter","first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","volume":16,"date_updated":"2023-08-10T22:30:51Z","oa":1,"publication_identifier":{"eissn":["17502799"],"issn":["17542189"]},"pmid":1,"_id":"9438","project":[{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"grant_number":"V00739","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","name":"Structural plasticity at mossy fiber-CA3 synapses","call_identifier":"FWF"}],"quality_controlled":"1","oa_version":"Submitted Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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.","month":"06","article_type":"original","date_published":"2021-06-01T00:00:00Z","scopus_import":"1","publisher":"Springer Nature","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"PeJo"}],"date_created":"2021-05-30T22:01:24Z","file":[{"date_updated":"2021-12-02T23:30:05Z","access_level":"open_access","file_name":"VandaeletalAuthorVersion2021.pdf","embargo":"2021-12-01","file_size":38574802,"date_created":"2021-07-08T12:27:55Z","checksum":"7eb580abd8893cdb0b410cf41bc8c263","content_type":"application/pdf","relation":"main_file","creator":"cziletti","file_id":"9639"}],"day":"01","type":"journal_article","intvolume":"        16","status":"public","publication":"Nature Protocols","issue":"6","file_date_updated":"2021-12-02T23:30:05Z","page":"2947–2967"}]