[{"file":[{"access_level":"open_access","date_updated":"2025-04-23T14:02:08Z","file_size":8192355,"checksum":"30098b4f0209556ddfb3540a23d07ca5","date_created":"2025-04-23T14:02:08Z","relation":"main_file","file_name":"2024_Neuron_Chen.pdf","success":1,"file_id":"19614","creator":"dernst","content_type":"application/pdf"}],"file_date_updated":"2025-04-23T14:02:08Z","date_updated":"2026-09-21T22:30:33Z","year":"2024","month":"03","publisher":"Elsevier","volume":112,"fulldoi":"https://doi.org/10.1016/j.neuron.2023.12.002","pmid":1,"doi":"10.1016/j.neuron.2023.12.002","article_processing_charge":"Yes (via OA deal)","abstract":[{"text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.","lang":"eng"}],"department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"author":[{"last_name":"Chen","first_name":"JingJing","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, JingJing"},{"first_name":"Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"first_name":"Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","last_name":"Chen","full_name":"Chen, Chong"},{"last_name":"Arai","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","first_name":"Itaru","full_name":"Arai, Itaru"},{"id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2344-1039","first_name":"Olena","last_name":"Kim","full_name":"Kim, Olena"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas"}],"page":"755-771.e9","issue":"5","_id":"14843","language":[{"iso":"eng"}],"external_id":{"isi":["001202925700001"],"pmid":["38215739"]},"ddc":["570"],"intvolume":"       112","oa":1,"has_accepted_license":"1","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"grant_number":"25383","_id":"26B66A3E-B435-11E9-9278-68D0E5697425","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse"}],"citation":{"short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron 112 (2024) 755–771.e9.","apa":"Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38; Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>","ieee":"J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” <i>Neuron</i>, vol. 112, no. 5. Elsevier, p. 755–771.e9, 2024.","ista":"Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. 2024. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 112(5), 755–771.e9.","ama":"Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. 2024;112(5):755-771.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>","chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>.","mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, vol. 112, no. 5, Elsevier, 2024, p. 755–771.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>."},"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.","related_material":{"record":[{"id":"15101","relation":"dissertation_contains","status":"public"}],"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/"}]},"type":"journal_article","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"isi":1,"corr_author":"1","day":"06","date_created":"2024-01-21T23:00:56Z","scopus_import":"1","article_type":"original","ec_funded":1,"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","oa_version":"Published Version","date_published":"2024-03-06T00:00:00Z","PlanS_conform":"1","quality_controlled":"1","publication_identifier":{"issn":["0896-6273"],"eissn":["1097-4199"]},"OA_place":"publisher","OA_type":"hybrid","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"publication":"Neuron","publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public"},{"supervisor":[{"last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"}],"author":[{"first_name":"JingJing","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","last_name":"Chen","full_name":"Chen, JingJing"}],"page":"84","article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"PeJo"}],"abstract":[{"text":"The coupling between presynaptic Ca2+ channels and release sensors is a key factor that\r\ndetermines speed and efficacy of synapse transmission. At some excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development, and tightening is often\r\nassociated with a switch in the reliance on different Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains unknown, and it is unclear how it changes\r\nduring development. To address this question, we analyzed the coupling configuration at the\r\ncerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of BC–PC indicated that release probability decreased, while the\r\nnumber of functional sites increased during development. Although transmitter release\r\npersistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic action potentials became shorter during development, suggesting reduced\r\nefficacy of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas docked vesicles were only clustered at later\r\ndevelopmental stages. The number of functional release sites correlated better with the AZ\r\nnumber early in development, but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling suggested a developmental transformation from a more random to a more\r\nclustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic\r\ntransmission.","lang":"eng"}],"doi":"10.15479/at:ista:15101","ddc":["570"],"oa":1,"has_accepted_license":"1","language":[{"iso":"eng"}],"_id":"15101","date_updated":"2026-04-07T13:24:22Z","file_date_updated":"2024-04-02T22:30:03Z","file":[{"date_created":"2024-03-11T14:10:58Z","file_name":"Thesis_Jingjing CHEN.docx","relation":"source_file","file_id":"15104","creator":"jchen","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","date_updated":"2024-04-02T22:30:03Z","embargo_to":"open_access","file_size":11271363,"checksum":"db4947474ffa271e66c254b6fe876a55"},{"embargo":"2024-04-01","checksum":"a5eeae8b5702cd540f5d03469bc33dde","file_size":16627311,"access_level":"open_access","date_updated":"2024-04-02T22:30:03Z","content_type":"application/pdf","file_id":"15105","creator":"jchen","relation":"main_file","file_name":"Thesis_Jingjing CHEN_merged.pdf","date_created":"2024-03-11T14:11:06Z"}],"fulldoi":"https://doi.org/10.15479/at:ista:15101","alternative_title":["ISTA Thesis"],"year":"2024","month":"03","publisher":"Institute of Science and Technology Austria","date_published":"2024-03-11T00:00:00Z","ec_funded":1,"degree_awarded":"PhD","title":"Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse","oa_version":"Published Version","publication_status":"published","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","status":"public","acknowledged_ssus":[{"_id":"EM-Fac"}],"OA_place":"publisher","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"14843"}]},"citation":{"short":"J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science and Technology Austria, 2024.","apa":"Chen, J. (2024). <i>Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>","ieee":"J. Chen, “Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse,” Institute of Science and Technology Austria, 2024.","ista":"Chen J. 2024. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria.","ama":"Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>","chicago":"Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>.","mla":"Chen, JingJing. <i>Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>."},"project":[{"call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","grant_number":"25383","_id":"26B66A3E-B435-11E9-9278-68D0E5697425"}],"day":"11","date_created":"2024-03-11T10:09:54Z","corr_author":"1","type":"dissertation","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"}}]