%0 Journal Article %T Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules %+ The Hospital for sick children [Toronto] (SickKids) %+ University of Toronto %+ The Jikei University School of Medicine %+ Ruhr University Bochum (RUB) %+ Imagerie dynamique du Neurone %A Fekete, Adam %A Nakamura, Yukihiro %A Yang, Yi-Mei %A Herlitze, Stefan %A Mark, Melanie D. %A Digregorio, David %A Wang, Lu-Yang %Z This work is supported by Operating Grants from the Canadian Institutes of HealthResearch (MOP-77610, MOP-81159, MOP-14692, VIH-105441), Natural Sciences andEngineering Research Council of Canada (Discovery Grant, RGPIN-2017-06665) andCanada Research Chair to L.Y.W.; D.A.D. is supported by the Centre National de laRecherche Scientifique, Fondation pour la Recherche Medicale and the Agence Nationalede la Recherche (ANR-2010-BLANC-1411 and ANR-13-BSV4-0016), and his laboratoryis a member of the Bio-Psy Laboratory of Excellence. Y.N. was supported by the JapanSociety for the Promotion of Science (KAKENHI Grant JP17K07064) %< avec comité de lecture %@ 2041-1723 %J Nature Communications %I Nature Publishing Group %V 10 %N 1 %P 826 %8 2019-02-18 %D 2019 %R 10.1038/s41467-019-08452-2 %M 30778063 %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/NeurobiologyJournal articles %X Synaptic heterogeneity is widely observed but its underpinnings remain elusive. We addressed this issue using mature calyx of Held synapses whose numbers of bouton-like swellings on stalks of the nerve terminals inversely correlate with release probability (Pr). We examined presynaptic Ca2+ currents and transients, topology of fluorescently tagged knock-in Ca2+ channels, and Ca2+ channel-synaptic vesicle (SV) coupling distance using Ca2+ chelator and inhibitor of septin cytomatrix in morphologically diverse synapses. We found that larger clusters of Ca2+ channels with tighter coupling distance to SVs elevate Pr in stalks, while smaller clusters with looser coupling distance lower Pr in swellings. Septin is a molecular determinant of the differences in coupling distance. Supported by numerical simulations, we propose that varying the ensemble of two morphological modules containing distinct Ca2+ channel-SV topographies diversifies Pr in the terminal, thereby establishing a morpho-functional continuum that expands the coding capacity within a single synapse population. %G English %2 https://cnrs.hal.science/hal-02378980/document %2 https://cnrs.hal.science/hal-02378980/file/s41467-019-08452-2.pdf %L hal-02378980 %U https://cnrs.hal.science/hal-02378980 %~ PASTEUR %~ CNRS %~ ANR %~ FRM