Cited by 136Neuroscience and Neuropharmacology ResearchIon channel regulation and functionCellular transport and secretion

Distinct Nanoscale Calcium Channel and Synaptic Vesicle Topographies Contribute to the Diversity of Synaptic Function

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Rebola, Nelson, Reva, Maria, Kirizs, Tekla, Szoboszlay, Miklos, Lőrincz, Andrea, Moneron, Gael, Nusser, Zoltan, DiGregorio, David A.·2019·Neuron

Published version of a preprint

Abstract

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 Ca 2+ imaging, Ca 2+ 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.

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  1. Besag, J. (1977). Contribution to the discussion of Dr Ripley's paper. Journal of the Royal Statistical Society Series B 39, 193-195.

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Authors
Rebola, N., Reva, M., Kirizs, T., Szoboszlay, M., Lőrincz, A., Moneron, G., Nusser, Z., & DiGregorio, D. A.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • HUN-REN Institute of Experimental Medicine (HU)
Corresponding author
DiGregorio, David A.
Venue
Neuron
Publisher
Elsevier BV
Published
2019-11
Volume
104
Issue
4
Pages
693-710.e9
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2977087614
Cited by
136
References
103
Citations by year
2026: 8 · 2025: 22 · 2024: 27 · 2023: 16 · 2022: 19 · 2021: 22 · 2020: 19 · 2019: 3
FWCI
7.55
Type
journal article
Language
en
Update notices
erratum (2021-10-06)
Open access
Locations
  • Neuron (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • European Research Council (ERC-AG 787157)
  • National Research, Development and Innovation Office (14-1-2015-0155)
  • Agence Nationale de la Recherche (ANR-17-CE16-0026, ANR-13-BSV4-0016, ANR-17-CE16-0019, ANR-2010-BLANC-1411)
  • Centre National de la Recherche Scientifique
  • Fondation pour la Recherche Médicale
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
voltage-gated calcium channels, synaptic vesicles, synaptic efficacy, synaptic plasticity, Munc13-1, active zone, vesicle docking, reaction-diffusion modeling, neuromodulation, cerebellar synapses, immunogold electron microscopy
MeSH terms
Animals, Mice, Inbred BALB C, Mice, Inbred C57BL, Synaptic Transmission, Synapses, Synaptic Vesicles, Calcium Channels, Mice

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