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All-optical monitoring of excitation-secretion coupling demonstrates that SV2A functions downstream of evoked Ca2+ entry.


ABSTRACT: SV2A, an essential transporter-like synaptic vesicle protein, is a major target for antiepileptic drugs and a receptor for clostridial neurotoxins including Botox. While SV2A is required for normal levels of evoked neurotransmitter release, the mechanism underlying this role remains unclear. Here, we introduce a new chemogenetic approach for all-optical monitoring of excitation-secretion coupling, and we demonstrate its use in characterizing the SV2A knockout (KO) phenotype in cultured hippocampal neurons. This method employs the HaloTag system to target a robust small-molecule Ca2+ indicator, JF646 -BAPTA, to the presynaptic compartment. The far-red fluorescence of this indicator enables multiplexing with the fluorescent glutamate sensor iGluSnFR for detection of pre

SUBMITTER: Bradberry MM 

PROVIDER: S-EPMC8810609 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature