Nanoscale Structural Plasticity of the Active Zone Matrix Modulates Presynaptic Function

Oleg O. Glebov, Rachel E. Jackson, Christian M. Winterflood, Dylan M. Owen, Ellen A. Barker, Patrick Doherty, Helge Ewers, Juan Burrone

Research output: Contribution to journalArticle (Academic Journal)peer-review

39 Citations (Scopus)
253 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)2715-2728
Number of pages14
JournalCell Reports
Volume18
Issue number11
DOIs
Publication statusPublished - 14 Mar 2017

Keywords

  • synaptic plasticity
  • super-resolution microscopy

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