%0 Journal Article %T Distinct Nanoscale Calcium Channel and Synaptic Vesicle Topographies Contribute to the Diversity of Synaptic Function %+ Imagerie dynamique du Neurone %+ Hungarian Academy of Sciences (MTA) %A Rebola, Nelson %A Reva, Maria %A Kirizs, Tekla %A Szoboszlay, Miklos %A Lőrincz, Andrea %A Moneron, Gael %A Nusser, Zoltan %A Digregorio, David %Z This study was supported by the Centre National de la Recherche Scientifique, Fondation pour la Recherche Médicale (Equipe FRM), Agence Nationale de la Recherche (ANR-2010-BLANC-1411, ANR-13-BSV4-0016, ANR-17-CE16-0019, and ANR-17-CE16-0026), and Ile de France (Domaine d'Intérêt Majeur (DIM) MALINF: DIM120121). M.R. was supported by the Pasteur Paris University (PPU) doctoral program. The laboratory of D.A.D. is a member of the Bio-Psy Laboratory of Excellence. Z.N. is the recipient of a Hungarian National Research Development and Innovation Office Collaborative Research Grant (VKSz 14-1-2015-0155), a European Research Council Advanced Grant (ERC-AG 787157), and a Hungarian National Brain Research Program Grant (NAP2.0). %< avec comité de lecture %@ 0896-6273 %J Neuron %I Elsevier %V 104 %N 4 %P 693-710.e9 %8 2019-11-20 %D 2019 %R 10.1016/j.neuron.2019.08.014 %M 31558350 %K Monte Carlo simulation %K active zone %K calcium-release coupling %K electron microscopy %K molecular nanotopography %K multi-photon imaging %K neuromodulation %K release probability %K synapse diversity %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X The nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+ imaging, Ca2+ chelator competition, immunogold electron microscopic (EM) localization of VGCCs and the active zone (AZ) protein Munc13-1, at two cerebellar synapses. Unexpectedly, we found that weak synapses exhibited 3-fold more VGCCs than strong synapses, while the coupling distance was 5-fold longer. Reaction-diffusion modeling could explain both functional and structural data with two strikingly different nanotopographical motifs: strong synapses are composed of SVs that are tightly coupled (∼10 nm) to VGCC clusters, whereas at weak synapses VGCCs were excluded from the vicinity (∼50 nm) of docked vesicles. The distinct VGCC-SV topographical motifs also confer differential sensitivity to neuromodulation. Thus, VGCC-SV arrangements are not canonical, and their diversity could underlie functional heterogeneity across CNS synapses. %G English %L hal-02378737 %U https://cnrs.hal.science/hal-02378737 %~ PASTEUR %~ CNRS %~ ANR %~ TEST3-HALCNRS %~ FRM