{"acknowledged_ssus":[{"_id":"EM-Fac"}],"publisher":"Institute of Science and Technology Austria","oa":1,"file":[{"date_created":"2024-03-11T14:10:58Z","access_level":"closed","file_id":"15104","creator":"jchen","embargo_to":"open_access","file_size":11271363,"checksum":"db4947474ffa271e66c254b6fe876a55","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"Thesis_Jingjing CHEN.docx","date_updated":"2024-04-02T22:30:03Z","relation":"source_file"},{"content_type":"application/pdf","date_updated":"2024-04-02T22:30:03Z","relation":"main_file","file_name":"Thesis_Jingjing CHEN_merged.pdf","creator":"jchen","file_size":16627311,"access_level":"open_access","date_created":"2024-03-11T14:11:06Z","file_id":"15105","checksum":"a5eeae8b5702cd540f5d03469bc33dde","embargo":"2024-04-01"}],"file_date_updated":"2024-04-02T22:30:03Z","date_created":"2024-03-11T10:09:54Z","month":"03","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"grant_number":"Z00312","call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"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"}],"department":[{"_id":"GradSch"},{"_id":"PeJo"}],"year":"2024","language":[{"iso":"eng"}],"author":[{"first_name":"JingJing","last_name":"Chen","full_name":"Chen, JingJing","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87"}],"day":"11","license":"https://creativecommons.org/licenses/by/4.0/","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"publication_identifier":{"issn":["2663 - 337X"]},"ec_funded":1,"abstract":[{"lang":"eng","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."}],"oa_version":"Published Version","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.","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>.","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>","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>","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.","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>.","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."},"supervisor":[{"first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"has_accepted_license":"1","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","related_material":{"record":[{"id":"14843","relation":"part_of_dissertation","status":"public"}]},"ddc":["570"],"date_updated":"2024-04-03T07:33:48Z","status":"public","page":"84","publication_status":"published","type":"dissertation","degree_awarded":"PhD","title":"Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse","article_processing_charge":"No","date_published":"2024-03-11T00:00:00Z","doi":"10.15479/at:ista:15101","alternative_title":["ISTA Thesis"],"_id":"15101"}