title: Different presynaptic roles of synapsins at excitatory and inhibitory synapses.
abstract: The functions of synapsins were examined by characterizing the phenotype of mice in which all three synapsin genes were knocked out. Although these triple knock-out mice were viable and had normal brain anatomy, they exhibited a number of behavioral defects. Synaptic transmission was altered in cultured neurons from the hippocampus of knock-out mice. At excitatory synapses, loss of synapsins did not affect basal transmission evoked by single stimuli but caused a threefold increase in the rate of synaptic depression during trains of stimuli. This suggests that synapsins regulate the reserve pool of synaptic vesicles. This possibility was examined further by measuring synaptic vesicle density in living neurons transfected with green fluorescent protein-tagged synaptobrevin 2, a marker of synaptic vesicles. The relative amount of fluorescent synaptobrevin was substantially lower at synapses of knock-out neurons than of wild-type neurons. Electron microscopy also revealed a parallel reduction in the number of vesicles in the reserve pool of vesicles >150 nm away from the active zone at excitatory synapses. Thus, synapsins are required for maintaining vesicles in the reserve pool at excitatory synapses. In contrast, basal transmission at inhibitory synapses was reduced by loss of synapsins, but the kinetics of synaptic depression were unaffected. In these terminals, there was a mild reduction in the total number of synaptic vesicles, but this was not restricted to the reserve pool of vesicles. Thus, synapsins maintain the reserve pool of glutamatergic vesicles but regulate the size of the readily releasable pool of GABAergic vesicles.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gitler
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takagishi
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.forename: Yong
authors.initials: Y
authors.lastname: Ren
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Rodriguiz
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
authors.forename: George J
authors.initials: GJ
authors.lastname: Augustine
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology* / Q000648:ultrastructure; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D007858:Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D010641:Phenotype; D013569:Synapses / Q000145:classification / Q000502:physiology*; D016704:Synapsins / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D016704:Synapsins