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• W4226156763 endingPage "1019" @default.
• W4226156763 startingPage "1001" @default.
• W4226156763 abstract "Using postsynaptically tethered calcium sensor GCaMP, we investigated spontaneous synaptic transmission at individual active zones (AZs) at the Drosophila (both sexes) neuromuscular junction. Optical monitoring of GCaMP events coupled with focal electrical recordings of synaptic currents revealed hot spots of spontaneous transmission, which corresponded to transient states of elevated activity at selected AZs. The elevated spontaneous activity had two temporal components, one at a timescale of minutes and the other at a subsecond timescale. We developed a three-state model of AZ preparedness for spontaneous transmission and performed Monte Carlo simulations of the release process, which produced an accurate quantitative description of the variability and time course of spontaneous transmission at individual AZs. To investigate the mechanisms of elevated activity, we first focused on the protein complexin, which binds the SNARE protein complex and serves to clamp spontaneous fusion. Overexpression of Drosophila complexin largely abolished the high-activity states of AZs, while complexin deletion drastically promoted it. A mutation in the SNARE protein Syntaxin-1A had an effect similar to complexin deficiency, promoting the high-activity state. We next tested how presynaptic Ca2+ transients affect the states of elevated activity at individual AZs. We either blocked or promoted Ca2+ influx pharmacologically, and also promoted Ca2+ release from internal stores. These experiments coupled with computations revealed that Ca2+ transients can trigger bursts of spontaneous events from individual AZs or AZ clusters at a subsecond timescale. Together, our results demonstrated that spontaneous transmission is highly heterogeneous, with transient hot spots being regulated by the SNARE machinery and Ca2+SIGNIFICANCE STATEMENT Spontaneous synaptic transmission is a vital component of neuronal communication, since it regulates the neuronal development and plasticity. Our study demonstrated that spontaneous transmission is highly heterogeneous and that nerve terminals create transient hot spots of spontaneous release of neuronal transmitters. We show that these hot spots are regulated by the protein machinery mediating the release process and by calcium ions. These results contribute to our understanding of spontaneous synaptic transmission as a dynamic, plastic, and tightly regulated signaling mechanism and unravel fundamental biophysical properties of neuronal communication." @default.
• W4226156763 created "2022-05-05" @default.
• W4226156763 creator A5006461386 @default.
• W4226156763 creator A5018308279 @default.
• W4226156763 creator A5078374871 @default.
• W4226156763 date "2021-12-30" @default.
• W4226156763 modified "2023-10-11" @default.
• W4226156763 title "Stochastic Properties of Spontaneous Synaptic Transmission at Individual Active Zones" @default.
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• W4226156763 doi "https://doi.org/10.1523/jneurosci.1162-21.2021" @default.
• W4226156763 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34969867" @default.
• W4226156763 hasPublicationYear "2021" @default.

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