{"date_updated":"2024-12-03T09:39:41Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","title":"Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons","status":"public","publication_identifier":{"eissn":["1545-7885"],"issn":["1544-9173"]},"language":[{"iso":"eng"}],"abstract":[{"text":"It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse.","lang":"eng"}],"volume":22,"year":"2024","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"intvolume":" 22","OA_place":"publisher","OA_type":"gold","issue":"11","day":"18","DOAJ_listed":"1","ddc":["570"],"type":"journal_article","citation":{"ista":"Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. 22(11), e3002879.","chicago":"Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto, and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” PLoS Biology. Public Library of Science, 2024. https://doi.org/10.1371/journal.pbio.3002879.","apa":"Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., & Jonas, P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3002879","ama":"Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. 2024;22(11). doi:10.1371/journal.pbio.3002879","short":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS Biology 22 (2024).","ieee":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,” PLoS Biology, vol. 22, no. 11. Public Library of Science, 2024.","mla":"Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” PLoS Biology, vol. 22, no. 11, e3002879, Public Library of Science, 2024, doi:10.1371/journal.pbio.3002879."},"publication":"PLoS Biology","acknowledgement":"We thank Carolina Borges-Merjane, Jing-Jing Chen, Katharina Lichter, and Samuel Young for critically reading the manuscript; the Electron Microscopy Facility of ISTA, in particular Vanessa Zheden, for extensive support, advice, and experimental assistance; the Preclinical Facility of ISTA, in particular Victoria Wimmer and Michael Schunn, for experimental assistance; Florian Marr and Christina Altmutter for technical support; Alois Schlögl for help with analysis; and Eleftheria Kralli-Beller for manuscript editing. We also thank Cordelia Imig for providing Munc13-1cKO-Munc13-2/3(−/−) mutant mice. Part of the work has been published in O.K.’s thesis in partial fulfillment of the requirements for the degree of Doctor of Philosophy.\r\nThis project received funding from the European Research Council and European Union’s Horizon 2020 research and innovation programme (ERC 692692 to P.J.; https://cordis.europa.eu/project/id/692692/de) and from the Fond zur Förderung der Wissenschaftlichen Forschung (Z312-B27 Wittgenstein award to P.J., https://www.fwf.ac.at/en/funding/portfolio/projects/fwf-wittgenstein-award; W1205-B09 and P36232-B to P.J., https://www.fwf.ac.at/en/funding; I6166-B to R.S.; https://www.fwf.ac.at/en/funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","file":[{"file_name":"2024_PloSBio_Kim.pdf","creator":"dernst","relation":"main_file","success":1,"file_size":3057631,"date_updated":"2024-12-03T08:56:53Z","date_created":"2024-12-03T08:56:53Z","access_level":"open_access","file_id":"18608","content_type":"application/pdf","checksum":"7de2dcb50deb65dde05c80082bb85a82"}],"publisher":"Public Library of Science","_id":"18603","author":[{"last_name":"Kim","first_name":"Olena","full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Okamoto, Yuji","id":"3337E116-F248-11E8-B48F-1D18A9856A87","last_name":"Okamoto","orcid":"0000-0003-0408-6094","first_name":"Yuji"},{"orcid":"0000-0001-9735-5315","first_name":"Walter","last_name":"Kaufmann","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","full_name":"Kaufmann, Walter"},{"last_name":"Brose","first_name":"Nils","full_name":"Brose, Nils"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444"},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"quality_controlled":"1","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"article_processing_charge":"Yes","ec_funded":1,"article_number":"e3002879","file_date_updated":"2024-12-03T08:56:53Z","doi":"10.1371/journal.pbio.3002879","date_created":"2024-12-01T23:01:54Z","oa":1,"date_published":"2024-11-18T00:00:00Z","license":"https://creativecommons.org/licenses/by/4.0/","article_type":"original","corr_author":"1","publication_status":"published","related_material":{"record":[{"relation":"research_data","status":"public","id":"18296"}]},"month":"11","has_accepted_license":"1","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","grant_number":"692692"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","call_identifier":"FWF","name":"Wittgenstein Award - Peter Jonas"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232"},{"_id":"b1b85715-d554-11ed-a5ad-84a07fc9f18e","name":"Structural & functional basis of presynaptic plasticity","grant_number":"I06166"},{"grant_number":"W01205","call_identifier":"FWF","name":"Zellkommunikation in Gesundheit und Krankheit","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425"}],"scopus_import":"1"}