{"day":"29","author":[{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444"}],"month":"07","date_created":"2023-06-29T13:16:42Z","year":"2023","oa":1,"license":"https://creativecommons.org/licenses/by-nc/4.0/","publisher":"Institute of Science and Technology Austria","abstract":[{"lang":"eng","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."}],"keyword":["medial habenula","GABAB receptor","vesicle release","Flash and Freeze","Flash and Freeze-fracture"],"date_published":"2023-07-29T00:00:00Z","status":"public","file":[{"date_created":"2023-06-29T13:11:22Z","title":"Outdated Version","file_size":542873672,"creator":"shigemot","access_level":"closed","date_updated":"2023-11-17T14:30:44Z","description":"After review an updated version of the data is provided","relation":"main_file","file_id":"13174","content_type":"application/x-zip-compressed","checksum":"ed59170869ba621f89f7c1894092192f","file_name":"Raw data for Koppensteiner et al.zip"},{"file_size":915079,"creator":"patrickd","access_level":"open_access","date_updated":"2023-11-17T14:13:02Z","success":1,"date_created":"2023-11-17T14:13:02Z","checksum":"c07860eb82b4d367245f1b589fe5c250","file_name":"11-17-23 Updated Koppensteiner et al. raw data.xlsx","file_id":"14550","relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet"},{"creator":"dernst","access_level":"open_access","date_updated":"2024-02-06T07:21:43Z","success":1,"file_size":544868924,"date_created":"2024-02-06T07:21:43Z","checksum":"abf84b1699edac4349dc3a92d466fb7b","file_name":"EM_Images.zip","content_type":"application/x-zip-compressed","relation":"main_file","file_id":"14942"}],"_id":"13173","ddc":["571"],"article_processing_charge":"No","title":"Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"15084"}]},"file_date_updated":"2024-02-06T07:21:43Z","citation":{"short":"R. Shigemoto, (2023).","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. <a href=\"https://doi.org/10.15479/AT:ISTA:13173\">https://doi.org/10.15479/AT:ISTA:13173</a>.","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. <a href=\"https://doi.org/10.15479/AT:ISTA:13173\">https://doi.org/10.15479/AT:ISTA:13173</a>","ama":"Shigemoto R. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. 2023. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13173\">10.15479/AT:ISTA:13173</a>","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.","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, <a href=\"https://doi.org/10.15479/AT:ISTA:13173\">10.15479/AT:ISTA:13173</a>.","mla":"Shigemoto, Ryuichi. <i>Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13173\">10.15479/AT:ISTA:13173</a>."},"tmp":{"image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2024-03-12T13:44:18Z","type":"research_data","oa_version":"Published Version","doi":"10.15479/AT:ISTA:13173","department":[{"_id":"RySh"}],"has_accepted_license":"1"}