期刊
JOURNAL OF NEUROSCIENCE
卷 34, 期 44, 页码 14687-14696出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2060-14.2014
关键词
granule cell; Munc13; release probability; superpriming; vesicular release
资金
- German Research Foundation research training group InterNeuro [1097]
- Collaborative Research Centre [889/B1]
- [SCHM1838/1]
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 (p(r)) 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 Ca2+ 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 Ca2+-triggered release.
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