[{"project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232"},{"grant_number":"25383","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","_id":"26B66A3E-B435-11E9-9278-68D0E5697425"}],"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","article_processing_charge":"No","external_id":{"pmid":["38215739"]},"author":[{"full_name":"Chen, JingJing","last_name":"Chen","first_name":"JingJing","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","last_name":"Kaufmann","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter"},{"first_name":"Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, Chong","last_name":"Chen"},{"full_name":"Arai, Itaru","last_name":"Arai","first_name":"Itaru","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kim","full_name":"Kim, Olena","first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron.","chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, n.d. https://doi.org/10.1016/j.neuron.2023.12.002.","apa":"Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., & Jonas, P. M. (n.d.). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002","ama":"Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. doi:10.1016/j.neuron.2023.12.002","ieee":"J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” Neuron. Elsevier.","short":"J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron (n.d.).","mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron, Elsevier, doi:10.1016/j.neuron.2023.12.002."},"publisher":"Elsevier","quality_controlled":"1","acknowledgement":"We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C.","date_created":"2024-01-21T23:00:56Z","date_published":"2024-01-11T00:00:00Z","doi":"10.1016/j.neuron.2023.12.002","publication":"Neuron","day":"11","year":"2024","status":"public","article_type":"original","type":"journal_article","_id":"14843","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"date_updated":"2024-03-14T13:14:18Z","month":"01","scopus_import":"1","oa_version":"None","pmid":1,"abstract":[{"lang":"eng","text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission."}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"ec_funded":1,"related_material":{"link":[{"description":"News on ISTA Website","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/","relation":"press_release"}],"record":[{"relation":"dissertation_contains","status":"public","id":"15101"}]},"language":[{"iso":"eng"}],"publication_status":"inpress","publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]}},{"ddc":["571"],"date_updated":"2023-09-20T11:32:15Z","department":[{"_id":"PeJo"}],"file_date_updated":"2018-12-12T10:16:09Z","_id":"1117","status":"public","pubrep_id":"751","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)"},"file":[{"creator":"system","file_size":4427591,"date_updated":"2018-12-12T10:16:09Z","file_name":"IST-2017-751-v1+1_1-s2.0-S2211124716317740-main.pdf","date_created":"2018-12-12T10:16:09Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"5195"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["22111247"]},"publication_status":"published","issue":"3","volume":18,"related_material":{"record":[{"id":"324","status":"public","relation":"dissertation_contains"}]},"license":"https://creativecommons.org/licenses/by/4.0/","ec_funded":1,"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"abstract":[{"text":"GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author","lang":"eng"}],"month":"01","intvolume":" 18","scopus_import":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ama":"Chen C, Arai itaru, Satterield R, Young S, Jonas PM. Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 2017;18(3):723-736. doi:10.1016/j.celrep.2016.12.067","apa":"Chen, C., Arai, itaru, Satterield, R., Young, S., & Jonas, P. M. (2017). Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2016.12.067","short":"C. Chen, itaru Arai, R. Satterield, S. Young, P.M. Jonas, Cell Reports 18 (2017) 723–736.","ieee":"C. Chen, itaru Arai, R. Satterield, S. Young, and P. M. Jonas, “Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse,” Cell Reports, vol. 18, no. 3. Cell Press, pp. 723–736, 2017.","mla":"Chen, Chong, et al. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” Cell Reports, vol. 18, no. 3, Cell Press, 2017, pp. 723–36, doi:10.1016/j.celrep.2016.12.067.","ista":"Chen C, Arai itaru, Satterield R, Young S, Jonas PM. 2017. Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 18(3), 723–736.","chicago":"Chen, Chong, itaru Arai, Rachel Satterield, Samuel Young, and Peter M Jonas. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2016.12.067."},"title":"Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse","publist_id":"6245","author":[{"first_name":"Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, Chong","last_name":"Chen"},{"full_name":"Arai, Itaru","last_name":"Arai","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","first_name":"Itaru"},{"first_name":"Rachel","full_name":"Satterield, Rachel","last_name":"Satterield"},{"first_name":"Samuel","full_name":"Young, Samuel","last_name":"Young"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"}],"article_processing_charge":"No","external_id":{"isi":["000396470600013"]},"project":[{"_id":"25C26B1E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P24909-B24","name":"Mechanisms of transmitter release at GABAergic synapses"},{"name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","grant_number":"268548","_id":"25C0F108-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"day":"17","publication":"Cell Reports","isi":1,"has_accepted_license":"1","year":"2017","date_published":"2017-01-17T00:00:00Z","doi":"10.1016/j.celrep.2016.12.067","date_created":"2018-12-11T11:50:14Z","page":"723 - 736","quality_controlled":"1","publisher":"Cell Press","oa":1},{"project":[{"grant_number":"P24909-B24","name":"Mechanisms of transmitter release at GABAergic synapses","call_identifier":"FWF","_id":"25C26B1E-B435-11E9-9278-68D0E5697425"},{"name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","grant_number":"268548","call_identifier":"FP7","_id":"25C0F108-B435-11E9-9278-68D0E5697425"}],"author":[{"first_name":"Itaru","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","full_name":"Arai, Itaru","last_name":"Arai"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"publist_id":"5041","title":"Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse","citation":{"mla":"Arai, itaru, and Peter M. Jonas. “Nanodomain Coupling Explains Ca^2+ Independence of Transmitter Release Time Course at a Fast Central Synapse.” ELife, vol. 3, eLife Sciences Publications, 2014, doi:10.7554/eLife.04057.","ama":"Arai itaru, Jonas PM. Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse. eLife. 2014;3. doi:10.7554/eLife.04057","apa":"Arai, itaru, & Jonas, P. M. (2014). Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.04057","ieee":"itaru Arai and P. M. Jonas, “Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse,” eLife, vol. 3. eLife Sciences Publications, 2014.","short":"itaru Arai, P.M. Jonas, ELife 3 (2014).","chicago":"Arai, itaru, and Peter M Jonas. “Nanodomain Coupling Explains Ca^2+ Independence of Transmitter Release Time Course at a Fast Central Synapse.” ELife. eLife Sciences Publications, 2014. https://doi.org/10.7554/eLife.04057.","ista":"Arai itaru, Jonas PM. 2014. Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse. eLife. 3."},"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","oa":1,"publisher":"eLife Sciences Publications","quality_controlled":"1","date_created":"2018-12-11T11:55:19Z","date_published":"2014-12-09T00:00:00Z","doi":"10.7554/eLife.04057","year":"2014","has_accepted_license":"1","publication":"eLife","day":"09","type":"journal_article","pubrep_id":"421","status":"public","_id":"2031","department":[{"_id":"PeJo"}],"file_date_updated":"2020-07-14T12:45:26Z","date_updated":"2021-01-12T06:54:51Z","ddc":["570"],"scopus_import":1,"intvolume":" 3","month":"12","abstract":[{"text":"A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o. Modeling of Ca2+-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca2+ channels and release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca2+]o independence of the time course of release.","lang":"eng"}],"oa_version":"Submitted Version","ec_funded":1,"volume":3,"publication_status":"published","language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","checksum":"c240f915450d4ebe8f95043a2a8c7b1a","file_id":"5094","file_size":2239563,"date_updated":"2020-07-14T12:45:26Z","creator":"system","file_name":"IST-2016-421-v1+1_e04057.full.pdf","date_created":"2018-12-12T10:14:41Z"}]}]