title: Munc13-3 superprimes synaptic vesicles at granule cell-to-basket cell synapses in the mouse cerebellum.
abstract: 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.
authors.affiliation: Carl Ludwig Institute for Physiology, Medical Faculty, University of Leipzig, D-04103 Leipzig, Germany, and.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Ishiyama
authors.affiliation: Carl Ludwig Institute for Physiology, Medical Faculty, University of Leipzig, D-04103 Leipzig, Germany, and.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany.
authors.forename: Benjamin H
authors.identifier: http://orcid.org/0000-0003-2374-9922
authors.initials: BH
authors.lastname: Cooper
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.affiliation: Carl Ludwig Institute for Physiology, Medical Faculty, University of Leipzig, D-04103 Leipzig, Germany, and jens.eilers@medizin.uni-leipzig.de.
authors.forename: Jens
authors.identifier: http://orcid.org/0000-0003-0497-5625
authors.initials: J
authors.lastname: Eilers
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C485550:Unc13c protein, mouse; D002118:Calcium
keywords: Munc13; granule cell; release probability; superpriming; vesicular release