Munc13-3 superprimes synaptic vesicles at granule cell-to-basket cell synapses in the mouse cerebellum.

Munc13-3 is a presynaptic protein implicated in vesicle priming that is strongly expressed in cerebellar granule cells (GCs). Mice deficient of Munc13-3 (Munc13-3(-/-)) show an increased paired-pulse ratio (PPR), which led to the hypothesis that Munc13-3 increases the release probability (pr) of vesicles. In the present study, we analyzed unitary synaptic connections between GCs and basket cells in acute cerebellar slices from wild-type and Munc13-3(-/-) mice. Unitary EPSCs recorded from Munc13-3(-/-) GCs showed normal kinetics and synaptic latency but a significantly increased PPR and fraction of synaptic failures. A quantal analysis revealed that neither the charge of single quanta nor the binominal parameter N were affected by loss of Munc13-3 but that pr was almost halved in Munc13-3(-/-). Neither presynaptic Ca(2+) influx was affected by deletion of Munc13-3 nor replenishment of the readily releasable vesicle pool. However, a high concentration of EGTA led to a reduction in EPSCs that was significantly stronger in Munc13-3(-/-). We conclude that Munc13-3 is responsible for an additional step of molecular and/or positional "superpriming" that substantially increases the efficacy of Ca(2+)-triggered release. Copyright © 2014 the authors 0270-6474/14/3414687-10$15.00/0.

Citation

Shimpei Ishiyama, Hartmut Schmidt, Benjamin H Cooper, Nils Brose, Jens Eilers. Munc13-3 superprimes synaptic vesicles at granule cell-to-basket cell synapses in the mouse cerebellum. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2014 Oct 29;34(44):14687-96

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PMID: 25355221

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