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Independent regulation of Basal neurotransmitter release efficacy by variable Ca²+ influx and bouton size at small central synapses.

Ermolyuk, YS; Alder, FG; Henneberger, C; Rusakov, DA; Kullmann, DM; Volynski, KE; (2012) Independent regulation of Basal neurotransmitter release efficacy by variable Ca²+ influx and bouton size at small central synapses. PLoS Biology , 10 (9) , Article e1001396. 10.1371/journal.pbio.1001396. Green open access

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Abstract

The efficacy of action potential evoked neurotransmitter release varies widely even among synapses supplied by the same axon, and the number of release-ready vesicles at each synapse is a major determinant of this heterogeneity. Here we identify a second, equally important, mechanism for release heterogeneity at small hippocampal synapses, the inter-synaptic variation of the exocytosis probability of release-ready vesicles. Using concurrent measurements of vesicular pool sizes, vesicular exocytosis rates, and presynaptic Ca²⁺ dynamics, in the same small hippocampal boutons, we show that the average fusion probability of release-ready vesicles varies among synapses supplied by the same axon with the size of the spike-evoked Ca²⁺ concentration transient. We further show that synapses with a high vesicular release probability exhibit a lower Ca²⁺ cooperativity, arguing that this is a direct consequence of increased Ca²⁺ influx at the active zone. We conclude that variability of neurotransmitter release under basal conditions at small central synapses is accounted for not only by the number of release-ready vesicles, but also by their fusion probabilities, which are set independently of bouton size by variable spike-evoked presynaptic Ca²⁺ influx.

Type: Article
Title: Independent regulation of Basal neurotransmitter release efficacy by variable Ca²+ influx and bouton size at small central synapses.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pbio.1001396
Publisher version: http://dx.doi.org/10.1371/journal.pbio.1001396
Language: English
Additional information: © Ermolyuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The study was supported by the Medical Research Council United Kingdom (G0600089), the Brain Research Trust, the Wellcome Trust (WT084311), the European Research Council, and a UCL Bridging Award for CH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. (PMCID: PMC3457933)
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
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
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
URI: https://discovery.ucl.ac.uk/id/eprint/1368858
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