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Nanoscale Structural Plasticity of the Active Zone Matrix Modulates Presynaptic Function.


ABSTRACT: The active zone (AZ) matrix of presynaptic terminals coordinates the recruitment of voltage-gated calcium channels (VGCCs) and synaptic vesicles to orchestrate neurotransmitter release. However, the spatial organization of the AZ and how it controls vesicle fusion remain poorly understood. Here, we employ super-resolution microscopy and ratiometric imaging to visualize the AZ structure on the nanoscale, revealing segregation between the AZ matrix, VGCCs, and putative release sites. Long-term blockade of neuronal activity leads to reversible AZ matrix unclustering and presynaptic actin depolymerization, allowing for enrichment of AZ machinery. Conversely, patterned optogenetic stimulation of postsynaptic neurons retrogradely enhanced AZ clustering. In individual synapses, AZ clustering was inversely correlated with local VGCC recruitment and vesicle cycling. Acute actin depolymerization led to rapid (5 min) nanoscale AZ matrix unclustering. We propose a model whereby neuronal activity modulates presynaptic function in a homeostatic manner by altering the clustering state of the AZ matrix.

SUBMITTER: Glebov OO 

PROVIDER: S-EPMC5368346 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Nanoscale Structural Plasticity of the Active Zone Matrix Modulates Presynaptic Function.

Glebov Oleg O OO   Jackson Rachel E RE   Winterflood Christian M CM   Owen Dylan M DM   Barker Ellen A EA   Doherty Patrick P   Ewers Helge H   Burrone Juan J  

Cell reports 20170301 11


The active zone (AZ) matrix of presynaptic terminals coordinates the recruitment of voltage-gated calcium channels (VGCCs) and synaptic vesicles to orchestrate neurotransmitter release. However, the spatial organization of the AZ and how it controls vesicle fusion remain poorly understood. Here, we employ super-resolution microscopy and ratiometric imaging to visualize the AZ structure on the nanoscale, revealing segregation between the AZ matrix, VGCCs, and putative release sites. Long-term blo  ...[more]

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