{"article_number":"e2301449121","external_id":{"pmid":["38346189"]},"_id":"15084","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"file_date_updated":"2024-03-12T13:42:42Z","author":[{"orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter","first_name":"Peter"},{"orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","last_name":"Bhandari","full_name":"Bhandari, Pradeep","first_name":"Pradeep"},{"orcid":"0000-0002-2771-2011","id":"4659D740-F248-11E8-B48F-1D18A9856A87","full_name":"Önal, Hüseyin C","last_name":"Önal","first_name":"Hüseyin C"},{"first_name":"Carolina","last_name":"Borges Merjane","full_name":"Borges Merjane, Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0005-401X"},{"id":"3B59276A-F248-11E8-B48F-1D18A9856A87","full_name":"Le Monnier, Elodie","last_name":"Le Monnier","first_name":"Elodie"},{"full_name":"Roy, Utsa","last_name":"Roy","first_name":"Utsa","id":"4d26cf11-5355-11ee-ae5a-eb05e255b9b2"},{"full_name":"Nakamura, Yukihiro","last_name":"Nakamura","first_name":"Yukihiro"},{"last_name":"Sadakata","full_name":"Sadakata, Tetsushi","first_name":"Tetsushi"},{"last_name":"Sanbo","full_name":"Sanbo, Makoto","first_name":"Makoto"},{"full_name":"Hirabayashi, Masumi","last_name":"Hirabayashi","first_name":"Masumi"},{"first_name":"JeongSeop","last_name":"Rhee","full_name":"Rhee, JeongSeop"},{"first_name":"Nils","full_name":"Brose, Nils","last_name":"Brose"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"}],"intvolume":"       121","acknowledgement":"We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support.","quality_controlled":"1","article_processing_charge":"Yes (in subscription journal)","doi":"10.1073/pnas.2301449121","department":[{"_id":"RySh"},{"_id":"PeJo"}],"publication_status":"published","month":"02","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles","oa":1,"date_created":"2024-03-05T09:23:55Z","issue":"8","pmid":1,"type":"journal_article","language":[{"iso":"eng"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","citation":{"apa":"Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. <i>Proceedings of the National Academy of Sciences</i>. Proceedings of the National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>","chicago":"Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences</i>. Proceedings of the National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>.","ama":"Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. <i>Proceedings of the National Academy of Sciences</i>. 2024;121(8). doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>","ista":"Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. 121(8), e2301449121.","ieee":"P. Koppensteiner <i>et al.</i>, “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” <i>Proceedings of the National Academy of Sciences</i>, vol. 121, no. 8. Proceedings of the National Academy of Sciences, 2024.","short":"P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences 121 (2024).","mla":"Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences</i>, vol. 121, no. 8, e2301449121, Proceedings of the National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>."},"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 (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n            <jats:sup>2+</jats:sup>\r\n            -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. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and 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 persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals."}],"file":[{"date_updated":"2024-03-12T13:42:42Z","success":1,"creator":"dernst","access_level":"open_access","file_name":"2024_PNAS_Koppensteiner.pdf","checksum":"b25b2a057c266ff317a48b0d54d6fc8a","content_type":"application/pdf","file_size":13648221,"relation":"main_file","file_id":"15110","date_created":"2024-03-12T13:42:42Z"}],"tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"date_published":"2024-02-20T00:00:00Z","oa_version":"Published Version","project":[{"name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"}],"year":"2024","volume":121,"ddc":["570"],"status":"public","day":"20","related_material":{"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/"}],"record":[{"id":"13173","status":"public","relation":"research_data"}]},"publication":"Proceedings of the National Academy of Sciences","article_type":"original","date_updated":"2024-10-21T06:01:13Z","corr_author":"1","publisher":"Proceedings of the National Academy of Sciences","has_accepted_license":"1","scopus_import":"1","ec_funded":1,"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"EM-Fac"}]}