| First Author | Ishiyama S | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 44 | Pages | 14687-96 |
| PubMed ID | 25355221 | Mgi Jnum | J:217424 |
| Mgi Id | MGI:5613871 | Doi | 10.1523/JNEUROSCI.2060-14.2014 |
| Citation | Ishiyama S, et al. (2014) Munc13-3 superprimes synaptic vesicles at granule cell-to-basket cell synapses in the mouse cerebellum. J Neurosci 34(44):14687-96 |
| abstractText | 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. |
