Nanoscale Structural Plasticity of the Active Zone Matrix Modulates Presynaptic Function

TY - JOUR

T1 - Nanoscale Structural Plasticity of the Active Zone Matrix Modulates Presynaptic Function

AU - Glebov, Oleg O.

AU - Jackson, Rachel E.

AU - Winterflood, Christian M.

AU - Owen, Dylan M.

AU - Barker, Ellen A.

AU - Doherty, Patrick

AU - Ewers, Helge

AU - Burrone, Juan

PY - 2017/3/14

Y1 - 2017/3/14

N2 - 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.

AB - 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.

KW - super-resolution microscopy

KW - synaptic plasticity

UR - http://www.scopus.com/inward/record.url?scp=85015162322&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.02.064

DO - 10.1016/j.celrep.2017.02.064

M3 - Article

SN - 2211-1247

VL - 18

SP - 2715

EP - 2728

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -