[{"page":"4197-4216","date_published":"2023-06-07T00:00:00Z","doi":"10.1523/JNEUROSCI.1514-22.2023","date_created":"2023-07-09T22:01:12Z","isi":1,"has_accepted_license":"1","year":"2023","day":"07","publication":"The Journal of Neuroscience","publisher":"Society for Neuroscience","quality_controlled":"1","oa":1,"acknowledgement":"This work was supported by The Institute of Science and Technology (IST) Austria, the European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. 793482 (to K.E.) and by the European Research Council (ERC) Grant Agreement No. 694539 (to R.S.). We thank Nicoleta Condruz (IST Austria, Klosterneuburg, Austria) for technical assistance with sample preparation, the Electron Microscopy Facility of IST Austria (Klosterneuburg, Austria) for technical support with EM works, Natalia Baranova (University of Vienna, Vienna, Austria) and Martin Loose (IST Austria, Klosterneuburg, Austria) for advice on liposome preparation, and Yugo Fukazawa (University of Fukui, Fukui, Japan) for comments.","author":[{"orcid":"0000-0002-6170-2546","full_name":"Eguchi, Kohgaku","last_name":"Eguchi","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","first_name":"Kohgaku"},{"full_name":"Le Monnier, Elodie","last_name":"Le Monnier","first_name":"Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi"}],"external_id":{"pmid":["37160366"],"isi":["001020132100005"]},"article_processing_charge":"No","title":"Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons","citation":{"mla":"Eguchi, Kohgaku, et al. “Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.” The Journal of Neuroscience, vol. 43, no. 23, Society for Neuroscience, 2023, pp. 4197–216, doi:10.1523/JNEUROSCI.1514-22.2023.","ama":"Eguchi K, Le Monnier E, Shigemoto R. Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. 2023;43(23):4197-4216. doi:10.1523/JNEUROSCI.1514-22.2023","apa":"Eguchi, K., Le Monnier, E., & Shigemoto, R. (2023). Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1514-22.2023","short":"K. Eguchi, E. Le Monnier, R. Shigemoto, The Journal of Neuroscience 43 (2023) 4197–4216.","ieee":"K. Eguchi, E. Le Monnier, and R. Shigemoto, “Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons,” The Journal of Neuroscience, vol. 43, no. 23. Society for Neuroscience, pp. 4197–4216, 2023.","chicago":"Eguchi, Kohgaku, Elodie Le Monnier, and Ryuichi Shigemoto. “Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.” The Journal of Neuroscience. Society for Neuroscience, 2023. https://doi.org/10.1523/JNEUROSCI.1514-22.2023.","ista":"Eguchi K, Le Monnier E, Shigemoto R. 2023. Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. 43(23), 4197–4216."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"call_identifier":"H2020","_id":"2659CC84-B435-11E9-9278-68D0E5697425","grant_number":"793482","name":"Ultrastructural analysis of phosphoinositides in nerve terminals: distribution, dynamics and physiological roles in synaptic transmission"},{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"issue":"23","volume":43,"ec_funded":1,"publication_identifier":{"issn":["0270-6474"],"eissn":["1529-2401"]},"publication_status":"published","file":[{"date_created":"2023-07-10T09:04:58Z","file_name":"2023_JN_Eguchi.pdf","date_updated":"2023-07-10T09:04:58Z","file_size":7794425,"creator":"alisjak","checksum":"70b2141870e0bf1c94fd343e18fdbc32","file_id":"13205","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"language":[{"iso":"eng"}],"scopus_import":"1","month":"06","intvolume":" 43","acknowledged_ssus":[{"_id":"EM-Fac"}],"abstract":[{"text":"Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an essential role in neuronal activities through interaction with various proteins involved in signaling at membranes. However, the distribution pattern of PI(4,5)P2 and the association with these proteins on the neuronal cell membranes remain elusive. In this study, we established a method for visualizing PI(4,5)P2 by SDS-digested freeze-fracture replica labeling (SDS-FRL) to investigate the quantitative nanoscale distribution of PI(4,5)P2 in cryo-fixed brain. We demonstrate that PI(4,5)P2 forms tiny clusters with a mean size of ∼1000 nm2 rather than randomly distributed in cerebellar neuronal membranes in male C57BL/6J mice. These clusters show preferential accumulation in specific membrane compartments of different cell types, in particular, in Purkinje cell (PC) spines and granule cell (GC) presynaptic active zones. Furthermore, we revealed extensive association of PI(4,5)P2 with CaV2.1 and GIRK3 across different membrane compartments, whereas its association with mGluR1α was compartment specific. These results suggest that our SDS-FRL method provides valuable insights into the physiological functions of PI(4,5)P2 in neurons.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"department":[{"_id":"RySh"}],"file_date_updated":"2023-07-10T09:04:58Z","date_updated":"2023-10-18T07:12:47Z","ddc":["570"],"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":"13202"},{"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","status":"public","_id":"13126","file_date_updated":"2023-08-04T13:19:47Z","department":[{"_id":"JoDa"},{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"Bio"},{"_id":"RySh"}],"date_updated":"2024-02-21T12:18:19Z","ddc":["610"],"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 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"}],"oa_version":"Published Version","ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","contributor":[{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","last_name":"Michalska"},{"last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","last_name":"Velicky","orcid":"0000-0002-2340-7431"},{"last_name":"Stefanickova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"orcid":"0000-0002-8698-3823","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer"},{"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"},{"first_name":"Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech"},{"last_name":"Höftberger","first_name":"Romana"},{"orcid":"0000-0001-8635-0877","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"related_material":{"link":[{"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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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","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).","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"publisher":"Institute of Science and Technology Austria","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)","date_created":"2023-06-07T07:15:12Z","doi":"10.15479/AT:ISTA:13126","date_published":"2023-08-04T00:00:00Z","year":"2023","has_accepted_license":"1","day":"04"},{"related_material":{"record":[{"relation":"research_data","status":"public","id":"13126"}],"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}]},"ec_funded":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"publication_status":"epub_ahead","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","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"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_updated":"2024-02-21T12:18:18Z","status":"public","type":"journal_article","article_type":"original","_id":"14257","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","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.).","title":"Imaging brain tissue architecture across millimeter to nanometer scales","author":[{"last_name":"Michalska","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","full_name":"Korinkova, Hana","last_name":"Korinkova"},{"orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"first_name":"Romana","last_name":"Höftberger","full_name":"Höftberger, Romana"},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"article_processing_charge":"Yes (in subscription journal)","external_id":{"isi":["001065254200001"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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","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).","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.","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.","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."},"project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"}]},{"_id":"13173","keyword":["medial habenula","GABAB receptor","vesicle release","Flash and Freeze","Flash and Freeze-fracture"],"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"type":"research_data","ddc":["571"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2024-03-12T13:44:18Z","citation":{"chicago":"Shigemoto, Ryuichi. “Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13173.","ista":"Shigemoto R. 2023. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals, Institute of Science and Technology Austria, 10.15479/AT:ISTA:13173.","mla":"Shigemoto, Ryuichi. Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals. Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13173.","ieee":"R. Shigemoto, “Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals.” Institute of Science and Technology Austria, 2023.","short":"R. Shigemoto, (2023).","ama":"Shigemoto R. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. 2023. doi:10.15479/AT:ISTA:13173","apa":"Shigemoto, R. (2023). Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:13173"},"file_date_updated":"2024-02-06T07:21:43Z","title":"Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals","department":[{"_id":"RySh"}],"article_processing_charge":"No","author":[{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","last_name":"Shigemoto"}],"oa_version":"Published Version","abstract":[{"text":"GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles at the presynaptic active zone (AZ). Strikingly, tonic and phasic release exhibit distinct coupling distances and are selectively affected by deletion of synaptoporin (SPO) and Ca2+-dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. Double pre-embedding immunolabeling confirmed the co-localization of CAPS2 and SPO inside the same terminal. The cytosolic protein CAPS2 showed a synaptic vesicle (SV)-associated distribution similar to the vesicular transmembrane protein SPO. A newly developed “Flash and Freeze-fracture” method revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to a persistent RRP increase. Thus, we discovered structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals.","lang":"eng"}],"month":"07","oa":1,"publisher":"Institute of Science and Technology Austria","day":"29","file":[{"file_name":"Raw data for Koppensteiner et al.zip","date_created":"2023-06-29T13:11:22Z","title":"Outdated Version","file_size":542873672,"date_updated":"2023-11-17T14:30:44Z","creator":"shigemot","checksum":"ed59170869ba621f89f7c1894092192f","file_id":"13174","description":"After review an updated version of the data is provided","content_type":"application/x-zip-compressed","relation":"main_file","access_level":"closed"},{"date_created":"2023-11-17T14:13:02Z","file_name":"11-17-23 Updated Koppensteiner et al. raw data.xlsx","creator":"patrickd","date_updated":"2023-11-17T14:13:02Z","file_size":915079,"file_id":"14550","checksum":"c07860eb82b4d367245f1b589fe5c250","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet"},{"content_type":"application/x-zip-compressed","access_level":"open_access","relation":"main_file","file_id":"14942","checksum":"abf84b1699edac4349dc3a92d466fb7b","success":1,"date_updated":"2024-02-06T07:21:43Z","file_size":544868924,"creator":"dernst","date_created":"2024-02-06T07:21:43Z","file_name":"EM_Images.zip"}],"year":"2023","has_accepted_license":"1","license":"https://creativecommons.org/licenses/by-nc/4.0/","date_created":"2023-06-29T13:16:42Z","doi":"10.15479/AT:ISTA:13173","related_material":{"record":[{"id":"15084","status":"public","relation":"used_in_publication"}]},"date_published":"2023-07-29T00:00:00Z"},{"date_created":"2022-03-20T23:01:39Z","doi":"10.3389/fnana.2022.846615","date_published":"2022-02-24T00:00:00Z","year":"2022","has_accepted_license":"1","isi":1,"publication":"Frontiers in Neuroanatomy","day":"24","oa":1,"publisher":"Frontiers","quality_controlled":"1","acknowledgement":"This work was supported by the European Research Council advanced grant No. 694539 and the joint German-Austrian DFG and FWF project SYNABS (FWF: I-4638-B) to RS.\r\nThe authors thank Walter Kaufmann for his critical comments on the manuscript.","article_processing_charge":"No","external_id":{"pmid":["35280978"],"isi":["000766662700001"]},"author":[{"full_name":"Eguchi, Kohgaku","orcid":"0000-0002-6170-2546","last_name":"Eguchi","first_name":"Kohgaku","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Montanaro-Punzengruber, Jacqueline-Claire","last_name":"Montanaro-Punzengruber","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","first_name":"Jacqueline-Claire"},{"first_name":"Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","full_name":"Le Monnier, Elodie","last_name":"Le Monnier"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi"}],"title":"The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals","citation":{"chicago":"Eguchi, Kohgaku, Jacqueline-Claire Montanaro-Punzengruber, Elodie Le Monnier, and Ryuichi Shigemoto. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy. Frontiers, 2022. https://doi.org/10.3389/fnana.2022.846615.","ista":"Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. 2022. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 16, 846615.","mla":"Eguchi, Kohgaku, et al. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy, vol. 16, 846615, Frontiers, 2022, doi:10.3389/fnana.2022.846615.","ieee":"K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, and R. Shigemoto, “The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals,” Frontiers in Neuroanatomy, vol. 16. Frontiers, 2022.","short":"K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, R. Shigemoto, Frontiers in Neuroanatomy 16 (2022).","apa":"Eguchi, K., Montanaro-Punzengruber, J.-C., Le Monnier, E., & Shigemoto, R. (2022). The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.846615","ama":"Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 2022;16. doi:10.3389/fnana.2022.846615"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour"},{"grant_number":"I04638","name":"LGI1 antibody-induced pathophysiology in synapses","_id":"05970B30-7A3F-11EA-A408-12923DDC885E"}],"article_number":"846615","ec_funded":1,"volume":16,"publication_status":"published","publication_identifier":{"eissn":["16625129"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2022-03-21T09:41:19Z","file_name":"2022_FrontiersNeuroanatomy_Eguchi.pdf","date_updated":"2022-03-21T09:41:19Z","file_size":2416395,"creator":"dernst","checksum":"51ec9b90e7da919e22c01a15489eaacd","file_id":"10911","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"scopus_import":"1","intvolume":" 16","month":"02","abstract":[{"text":"Upon the arrival of action potentials at nerve terminals, neurotransmitters are released from synaptic vesicles (SVs) by exocytosis. CaV2.1, 2.2, and 2.3 are the major subunits of the voltage-gated calcium channel (VGCC) responsible for increasing intraterminal calcium levels and triggering SV exocytosis in the central nervous system (CNS) synapses. The two-dimensional analysis of CaV2 distributions using sodium dodecyl sulfate (SDS)-digested freeze-fracture replica labeling (SDS-FRL) has revealed their numbers, densities, and nanoscale clustering patterns in individual presynaptic active zones. The variation in these properties affects the coupling of VGCCs with calcium sensors on SVs, synaptic efficacy, and temporal precision of transmission. In this study, we summarize how the morphological parameters of CaV2 distribution obtained using SDS-FRL differ depending on the different types of synapses and could correspond to functional properties in synaptic transmission.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"department":[{"_id":"RySh"}],"file_date_updated":"2022-03-21T09:41:19Z","date_updated":"2023-08-03T06:07:18Z","ddc":["570"],"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","status":"public","_id":"10890"}]