TY - JOUR T1 - Munc13-3 Superprimes Synaptic Vesicles at Granule Cell-to-Basket Cell Synapses in the Mouse Cerebellum JF - The Journal of Neuroscience JO - J. Neurosci. SP - 14687 LP - 14696 DO - 10.1523/JNEUROSCI.2060-14.2014 VL - 34 IS - 44 AU - Shimpei Ishiyama AU - Hartmut Schmidt AU - Benjamin H. Cooper AU - Nils Brose AU - Jens Eilers Y1 - 2014/10/29 UR - http://www.jneurosci.org/content/34/44/14687.abstract N2 - 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 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. ER -