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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)","title":"Research data for the publication \"Imaging brain tissue architecture across millimeter to nanometer scales\"","article_processing_charge":"No","author":[{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ieee":"J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales.’” Institute of Science and Technology Austria, 2023.","short":"J.G. Danzl, (2023).","ama":"Danzl JG. Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” 2023. doi:10.15479/AT:ISTA:13126","apa":"Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:13126","mla":"Danzl, Johann G. Research Data for the Publication “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13126.","ista":"Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:13126.","chicago":"Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.’” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13126."},"project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","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"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry"}],"contributor":[{"last_name":"Michalska","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik"},{"last_name":"Velicky","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp"},{"last_name":"Stefanickova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"last_name":"Watson","orcid":"0000-0002-8698-3823","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri"},{"last_name":"Sommer","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Amberg","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole"},{"orcid":"0000-0003-2356-9403","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro"},{"last_name":"Roessler","first_name":"Karl"},{"first_name":"Thomas","last_name":"Czech"},{"first_name":"Romana","last_name":"Höftberger"},{"last_name":"Siegert","orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804"}],"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","ec_funded":1,"related_material":{"record":[{"relation":"used_in_publication","id":"14257","status":"public"}],"link":[{"relation":"research_data","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. 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Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here, we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"file_date_updated":"2023-08-04T13:19:47Z","department":[{"_id":"JoDa"},{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"Bio"},{"_id":"RySh"}],"ddc":["610"],"date_updated":"2024-02-21T12:18:19Z","status":"public","tmp":{"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","short":"CC BY-NC-SA (4.0)"},"type":"research_data","_id":"13126"},{"publisher":"Springer Nature","quality_controlled":"1","oa":1,"acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","doi":"10.1038/s41587-023-01911-8","date_published":"2023-08-31T00:00:00Z","date_created":"2023-09-03T22:01:15Z","day":"31","publication":"Nature Biotechnology","isi":1,"year":"2023","project":[{"name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize"},{"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","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","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"},{"name":"International IST Doctoral Program","grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"}],"title":"Imaging brain tissue architecture across millimeter to nanometer scales","author":[{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","last_name":"Michalska"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","last_name":"Velicky"},{"last_name":"Korinkova","full_name":"Korinkova, Hana","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Roessler","full_name":"Roessler, Karl","first_name":"Karl"},{"full_name":"Czech, Thomas","last_name":"Czech","first_name":"Thomas"},{"full_name":"Höftberger, Romana","last_name":"Höftberger","first_name":"Romana"},{"orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"},{"last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"Yes (in subscription journal)","external_id":{"isi":["001065254200001"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8.","ieee":"J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.","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).","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8"},"month":"08","scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"oa_version":"Published Version","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"related_material":{"record":[{"relation":"research_data","status":"public","id":"13126"}],"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}]},"ec_funded":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"publication_status":"epub_ahead","status":"public","type":"journal_article","article_type":"original","_id":"14257","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"date_updated":"2024-02-21T12:18:18Z"},{"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","_id":"10763","department":[{"_id":"PeJo"}],"file_date_updated":"2022-02-21T07:59:32Z","ddc":["570"],"date_updated":"2023-08-02T14:25:33Z","intvolume":" 13","month":"02","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"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.","lang":"eng"}],"volume":13,"language":[{"iso":"eng"}],"file":[{"file_name":"2022_NatureCommunications_Herguedas.pdf","date_created":"2022-02-21T07:59:32Z","file_size":2625540,"date_updated":"2022-02-21T07:59:32Z","creator":"dernst","success":1,"checksum":"d86ee8eabe8b794730729ffbb1a8832e","file_id":"10778","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"publication_status":"published","publication_identifier":{"eissn":["20411723"]},"article_number":"734","title":"Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor","external_id":{"isi":["000757297200008"],"pmid":["35136046"]},"article_processing_charge":"No","author":[{"first_name":"Beatriz","full_name":"Herguedas, Beatriz","last_name":"Herguedas"},{"first_name":"Bianka K.","full_name":"Kohegyi, Bianka K.","last_name":"Kohegyi"},{"last_name":"Dohrke","full_name":"Dohrke, Jan Niklas","first_name":"Jan Niklas"},{"first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake"},{"full_name":"Zhang, Danyang","last_name":"Zhang","first_name":"Danyang"},{"full_name":"Ho, Hinze","last_name":"Ho","first_name":"Hinze"},{"last_name":"Shaikh","full_name":"Shaikh, Saher A.","first_name":"Saher A."},{"full_name":"Lape, Remigijus","last_name":"Lape","first_name":"Remigijus"},{"full_name":"Krieger, James M.","last_name":"Krieger","first_name":"James M."},{"first_name":"Ingo H.","full_name":"Greger, Ingo H.","last_name":"Greger"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ieee":"B. Herguedas et al., “Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor,” Nature Communications, vol. 13. Springer Nature, 2022.","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).","ama":"Herguedas B, Kohegyi BK, Dohrke JN, et al. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 2022;13. doi:10.1038/s41467-022-28404-7","apa":"Herguedas, B., Kohegyi, B. K., Dohrke, J. N., Watson, J., Zhang, D., Ho, H., … Greger, I. H. (2022). Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28404-7","mla":"Herguedas, Beatriz, et al. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” Nature Communications, vol. 13, 734, Springer Nature, 2022, doi:10.1038/s41467-022-28404-7.","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.","chicago":"Herguedas, Beatriz, Bianka K. Kohegyi, Jan Niklas Dohrke, Jake Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, and Ingo H. Greger. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28404-7."},"oa":1,"publisher":"Springer Nature","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).","date_created":"2022-02-20T23:01:30Z","date_published":"2022-02-08T00:00:00Z","doi":"10.1038/s41467-022-28404-7","publication":"Nature Communications","day":"08","year":"2022","has_accepted_license":"1","isi":1},{"oa":1,"publisher":"Springer Nature","quality_controlled":"1","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.).","date_created":"2022-08-24T08:25:50Z","date_published":"2022-08-16T00:00:00Z","doi":"10.1038/s41467-022-32559-8","year":"2022","isi":1,"has_accepted_license":"1","publication":"Nature Communications","day":"16","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"The Wittgenstein Prize"}],"article_number":"4826","article_processing_charge":"No","external_id":{"isi":["000841396400008"]},"author":[{"first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","full_name":"Ben Simon, Yoav"},{"full_name":"Käfer, Karola","last_name":"Käfer","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","first_name":"Karola"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431"},{"last_name":"Csicsvari","orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","first_name":"Jozsef L"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"}],"title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","citation":{"chicago":"Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32559-8.","ista":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 13, 4826.","mla":"Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications, vol. 13, 4826, Springer Nature, 2022, doi:10.1038/s41467-022-32559-8.","apa":"Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., & Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32559-8","ama":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 2022;13. doi:10.1038/s41467-022-32559-8","ieee":"Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M. Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory,” Nature Communications, vol. 13. Springer Nature, 2022.","short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022)."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 13","month":"08","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"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"oa_version":"Published Version","ec_funded":1,"volume":13,"publication_status":"published","publication_identifier":{"issn":["2041-1723"]},"language":[{"iso":"eng"}],"file":[{"success":1,"checksum":"405936d9e4d33625d80c093c9713a91f","file_id":"11990","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2022_NatureCommunications_BenSimon.pdf","date_created":"2022-08-26T11:51:40Z","creator":"dernst","file_size":5910357,"date_updated":"2022-08-26T11:51:40Z"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"status":"public","_id":"11951","file_date_updated":"2022-08-26T11:51:40Z","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"date_updated":"2023-08-03T13:01:19Z","ddc":["570"]},{"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"12463","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","success":1,"date_updated":"2023-01-30T11:50:53Z","file_size":8506811,"creator":"dernst","date_created":"2023-01-30T11:50:53Z","file_name":"2022_eLife_Sumser.pdf"}],"publication_status":"published","publication_identifier":{"eissn":["2050-084X"]},"ec_funded":1,"volume":11,"pmid":1,"oa_version":"Published Version","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"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"intvolume":" 11","month":"09","scopus_import":"1","ddc":["570"],"date_updated":"2023-08-04T10:29:48Z","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"file_date_updated":"2023-01-30T11:50:53Z","_id":"12288","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","publication":"eLife","day":"15","year":"2022","isi":1,"has_accepted_license":"1","date_created":"2023-01-16T10:04:15Z","date_published":"2022-09-15T00:00:00Z","doi":"10.7554/elife.79848","acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","oa":1,"quality_controlled":"1","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.79848.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” eLife, vol. 11. eLife Sciences Publications, 2022.","ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 2022;11. doi:10.7554/elife.79848","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.79848","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848."},"title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","article_processing_charge":"No","external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"author":[{"first_name":"Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4792-1881","full_name":"Sumser, Anton L","last_name":"Sumser"},{"first_name":"Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","last_name":"Jösch","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330"},{"last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"}],"article_number":"79848","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"2634E9D2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Circuits of Visual Attention","grant_number":"756502"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","grant_number":"LT000256","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"grant_number":"ALTF 1098-2017","name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425"}]},{"day":"20","year":"2022","has_accepted_license":"1","date_created":"2022-04-20T09:47:12Z","date_published":"2022-04-20T00:00:00Z","doi":"10.15479/at:ista:11196","page":"132","oa":1,"publisher":"Institute of Science and Technology Austria","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"mla":"Kim, Olena. Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11196.","apa":"Kim, O. (2022). Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11196","ama":"Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. 2022. doi:10.15479/at:ista:11196","short":"O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022.","ieee":"O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022.","chicago":"Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11196.","ista":"Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria."},"title":"Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses","article_processing_charge":"No","author":[{"last_name":"Kim","full_name":"Kim, Olena","first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"}],"project":[{"call_identifier":"H2020","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","grant_number":"708497","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse"},{"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","name":"Zellkommunikation in Gesundheit und Krankheit","call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize"}],"language":[{"iso":"eng"}],"file":[{"file_size":21273537,"date_updated":"2023-04-20T22:30:03Z","creator":"okim","file_name":"Olena_KIM_thesis_final.pdf","date_created":"2022-04-20T14:21:56Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","embargo":"2023-04-19","checksum":"1616a8bf6f13a57c892dac873dcd0936","file_id":"11220"},{"creator":"okim","date_updated":"2023-04-20T22:30:03Z","file_size":59248569,"date_created":"2022-04-20T14:22:56Z","file_name":"KIM_thesis_final.zip","access_level":"closed","relation":"source_file","content_type":"application/x-zip-compressed","embargo_to":"open_access","file_id":"11221","checksum":"1acb433f98dc42abb0b4b0cbb0c4b918"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"ec_funded":1,"related_material":{"record":[{"id":"11222","status":"public","relation":"part_of_dissertation"},{"id":"7473","status":"public","relation":"part_of_dissertation"}]},"oa_version":"Published Version","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"abstract":[{"text":"One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.\r\n","lang":"eng"}],"month":"04","alternative_title":["ISTA Thesis"],"ddc":["570"],"date_updated":"2023-08-18T06:31:52Z","supervisor":[{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"file_date_updated":"2023-04-20T22:30:03Z","department":[{"_id":"PeJo"},{"_id":"GradSch"}],"_id":"11196","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"dissertation"},{"abstract":[{"lang":"eng","text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue."}],"oa_version":"Preprint","publisher":"Cold Spring Harbor Laboratory","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.03.16.484431"}],"month":"05","publication_status":"submitted","year":"2022","day":"09","publication":"bioRxiv","language":[{"iso":"eng"}],"related_material":{"record":[{"id":"12470","status":"public","relation":"dissertation_contains"}]},"doi":"10.1101/2022.03.16.484431","date_published":"2022-05-09T00:00:00Z","date_created":"2022-08-23T11:07:59Z","_id":"11943","type":"preprint","status":"public","citation":{"ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","ieee":"P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431."},"date_updated":"2024-03-27T23:30:20Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp"},{"id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder","full_name":"Miguel Villalba, Eder","orcid":"0000-0001-5665-0430","last_name":"Miguel Villalba"},{"last_name":"Michalska","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"last_name":"Lin","full_name":"Lin, Zudi","first_name":"Zudi"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson"},{"first_name":"Jakob","full_name":"Troidl, Jakob","last_name":"Troidl"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","last_name":"Ben Simon"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","full_name":"Jahr, Wiebke","last_name":"Jahr"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Johannes","full_name":"Broichhagen, Johannes","last_name":"Broichhagen"},{"last_name":"Grant","full_name":"Grant, Seth G. N.","first_name":"Seth G. N."},{"last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"last_name":"Pfister","full_name":"Pfister, Hanspeter","first_name":"Hanspeter"},{"first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd"},{"last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"article_processing_charge":"No","title":"Saturated reconstruction of living brain tissue","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}]},{"main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"oa":1,"publisher":"Cold Spring Harbor Laboratory","month":"08","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"}],"oa_version":"Preprint","date_created":"2022-08-24T08:24:52Z","doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","related_material":{"record":[{"id":"12470","status":"public","relation":"dissertation_contains"}]},"year":"2022","publication_status":"submitted","publication":"bioRxiv","language":[{"iso":"eng"}],"day":"18","type":"preprint","status":"public","_id":"11950","article_processing_charge":"No","author":[{"orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp"},{"last_name":"Korinkova","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana"},{"full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Venturino","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Roessler","full_name":"Roessler, Karl","first_name":"Karl"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"}],"title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"date_updated":"2024-03-27T23:30:20Z","citation":{"chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272.","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272","ieee":"J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory.","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.)."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","_id":"9097","file_date_updated":"2021-02-09T07:33:23Z","department":[{"_id":"PeJo"}],"date_updated":"2022-08-19T07:22:23Z","ddc":["570"],"scopus_import":"1","month":"01","intvolume":" 11","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."}],"oa_version":"Published Version","volume":11,"publication_identifier":{"eissn":["20452322"]},"publication_status":"published","file":[{"success":1,"checksum":"e8a68df48750712671f5c47b0228e531","file_id":"9106","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2021_ScientificReports_Pandey.pdf","date_created":"2021-02-09T07:33:23Z","file_size":2885056,"date_updated":"2021-02-09T07:33:23Z","creator":"dernst"}],"language":[{"iso":"eng"}],"article_number":"2204","author":[{"last_name":"Pandey","full_name":"Pandey, Rakesh","first_name":"Rakesh"},{"first_name":"Yusur","last_name":"Al-Nuaimi","full_name":"Al-Nuaimi, Yusur"},{"id":"46CB58F2-F248-11E8-B48F-1D18A9856A87","first_name":"Rajiv Kumar","full_name":"Mishra, Rajiv Kumar","last_name":"Mishra"},{"last_name":"Spurgeon","full_name":"Spurgeon, Sarah K.","first_name":"Sarah K."},{"full_name":"Goodfellow, Marc","last_name":"Goodfellow","first_name":"Marc"}],"article_processing_charge":"No","title":"Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis","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.” Scientific Reports, vol. 11, 2204, Springer Nature, 2021, doi:10.1038/s41598-020-80507-7.","ieee":"R. Pandey, Y. Al-Nuaimi, R. K. Mishra, S. K. Spurgeon, and M. Goodfellow, “Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis,” Scientific Reports, vol. 11. Springer Nature, 2021.","short":"R. Pandey, Y. Al-Nuaimi, R.K. Mishra, S.K. Spurgeon, M. Goodfellow, Scientific Reports 11 (2021).","apa":"Pandey, R., Al-Nuaimi, Y., Mishra, R. K., Spurgeon, S. K., & Goodfellow, M. (2021). Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. Springer Nature. https://doi.org/10.1038/s41598-020-80507-7","ama":"Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 2021;11. doi:10.1038/s41598-020-80507-7","chicago":"Pandey, Rakesh, Yusur Al-Nuaimi, Rajiv Kumar Mishra, Sarah K. Spurgeon, and Marc Goodfellow. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports. Springer Nature, 2021. https://doi.org/10.1038/s41598-020-80507-7.","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Springer Nature","quality_controlled":"1","oa":1,"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).","doi":"10.1038/s41598-020-80507-7","date_published":"2021-01-26T00:00:00Z","date_created":"2021-02-07T23:01:12Z","has_accepted_license":"1","year":"2021","day":"26","publication":"Scientific Reports"},{"status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","article_type":"original","_id":"9329","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"file_date_updated":"2021-04-19T08:30:22Z","ddc":["570"],"date_updated":"2023-08-07T14:36:14Z","intvolume":" 357","month":"03","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.\r\nNew method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.\r\nResults: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.\r\nComparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.\r\nConclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity."}],"acknowledged_ssus":[{"_id":"SSU"}],"ec_funded":1,"volume":357,"issue":"6","language":[{"iso":"eng"}],"file":[{"file_id":"9339","checksum":"2a5800d91b96d08b525e17319dcd5e44","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2021-04-19T08:30:22Z","file_name":"2021_JourNeuroscienceMeth_Zhang.pdf","creator":"dernst","date_updated":"2021-04-19T08:30:22Z","file_size":6924738}],"publication_status":"published","publication_identifier":{"eissn":["1872-678X"],"issn":["0165-0270"]},"project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312"}],"article_number":"109125","title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","article_processing_charge":"Yes (via OA deal)","external_id":{"isi":["000661088500005"]},"author":[{"full_name":"Zhang, Xiaomin","last_name":"Zhang","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois","last_name":"Schlögl","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100"},{"first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","last_name":"Vandael","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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.” Journal of Neuroscience Methods. Elsevier, 2021. https://doi.org/10.1016/j.jneumeth.2021.109125.","ista":"Zhang X, Schlögl A, Vandael DH, Jonas PM. 2021. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 357(6), 109125.","mla":"Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods, vol. 357, no. 6, 109125, Elsevier, 2021, doi:10.1016/j.jneumeth.2021.109125.","ama":"Zhang X, Schlögl A, Vandael DH, Jonas PM. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 2021;357(6). doi:10.1016/j.jneumeth.2021.109125","apa":"Zhang, X., Schlögl, A., Vandael, D. H., & Jonas, P. M. (2021). MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. Elsevier. https://doi.org/10.1016/j.jneumeth.2021.109125","ieee":"X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo,” Journal of Neuroscience Methods, vol. 357, no. 6. Elsevier, 2021.","short":"X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021)."},"oa":1,"quality_controlled":"1","publisher":"Elsevier","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.","date_created":"2021-04-18T22:01:39Z","date_published":"2021-03-09T00:00:00Z","doi":"10.1016/j.jneumeth.2021.109125","publication":"Journal of Neuroscience Methods","day":"09","year":"2021","has_accepted_license":"1","isi":1}]