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- W2892314717 abstract "SUMMARY 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 modelling 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 across CNS synapses and their diversity could underlie functional heterogeneity." @default.
- W2892314717 created "2018-09-27" @default.
- W2892314717 creator A5005063877 @default.
- W2892314717 creator A5008837657 @default.
- W2892314717 creator A5018125160 @default.
- W2892314717 creator A5020661745 @default.
- W2892314717 creator A5046367950 @default.
- W2892314717 creator A5049565182 @default.
- W2892314717 creator A5065179137 @default.
- W2892314717 date "2018-09-20" @default.
- W2892314717 modified "2023-09-25" @default.
- W2892314717 title "Distinct nanoscale calcium channel and synaptic vesicle topographies contribute to the diversity of synaptic function" @default.
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