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Asynchronous glutamate release is enhanced in low release efficacy synapses and dispersed across the active zone

Mendonça, Philipe RF; Tagliatti, Erica; Langley, Helen; Kotzadimitriou, Dimitrios; Zamora-Chimal, Criseida G; Timofeeva, Yulia; Volynski, Kirill E; (2022) Asynchronous glutamate release is enhanced in low release efficacy synapses and dispersed across the active zone. Nature Communications , 13 , Article 3497. 10.1038/s41467-022-31070-4. Green open access

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Abstract

The balance between fast synchronous and delayed asynchronous release of neurotransmitters has a major role in defining computational properties of neuronal synapses and regulation of neuronal network activity. However, how it is tuned at the single synapse level remains poorly understood. Here, using the fluorescent glutamate sensor SF-iGluSnFR, we image quantal vesicular release in tens to hundreds of individual synaptic outputs from single pyramidal cells with 4 millisecond temporal and 75 nm spatial resolution. We find that the ratio between synchronous and asynchronous synaptic vesicle exocytosis varies extensively among synapses supplied by the same axon, and that the synchronicity of release is reduced at low release probability synapses. We further demonstrate that asynchronous exocytosis sites are more widely distributed within the release area than synchronous sites. Together, our results reveal a universal relationship between the two major functional properties of synapses – the timing and the overall efficacy of neurotransmitter release.

Type: Article
Title: Asynchronous glutamate release is enhanced in low release efficacy synapses and dispersed across the active zone
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-022-31070-4
Publisher version: https://doi.org/10.1038/s41467-022-31070-4
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/10150571
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