title: Rab3 superprimes synaptic vesicles for release: implications for short-term synaptic plasticity.
abstract: Presynaptic vesicle trafficking and priming are important steps in regulating synaptic transmission and plasticity. The four closely related small GTP-binding proteins Rab3A, Rab3B, Rab3C, and Rab3D are believed to be important for these steps. In mice, the complete absence of all Rab3s leads to perinatal lethality accompanied by a 30% reduction of probability of Ca2+-triggered synaptic release. This study examines the role of Rab3 during Ca2+-triggered release in more detail and identifies its impact on short-term plasticity. Using patch-clamp electrophysiology of autaptic neuronal cultures from Rab3-deficient mouse hippocampus, we show that excitatory Rab3-deficient neurons display unique time- and frequency-dependent short-term plasticity characteristics in response to spike trains. Analysis of vesicle release and repriming kinetics as well as Ca2+ sensitivity of release indicate that Rab3 acts on a subset of primed, fusion competent vesicles. They lower the amount of Ca2+ required for action potential-triggered release, which leads to a boosting of release probability, but their action also introduces a significant delay in the supply of these modified vesicles. As a result, Rab3-induced modifications to primed vesicles causes a transient increase in the transduction efficacy of synaptic action potential trains and optimizes the encoding of synaptic information at an intermediate spike frequency range.
authors.affiliation: Department of Neuroscience and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
authors.forename: Jayeeta
authors.initials: J
authors.lastname: Basu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenmund
mesh_terms: D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling; D002478:Cells, Cultured; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*; D013997:Time Factors; D020692:rab3 GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020826:rab3A GTP-Binding Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D002104:Cadmium; C116709:Rab3b protein, mouse; C486479:Rab3c protein, mouse; C116711:Rab3d protein, mouse; D020692:rab3 GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein; D002118:Calcium