SUSTAINED NEUROTRANSMITTER RELEASE - NEW MOLECULAR CLUES

Chemical synapses convey impulses at high frequency by exocytosis of s ynaptic vesicles. To avoid failure of synaptic transmission, rapid rep lenishment of synaptic vesicles must occur. Recent molecular perturbat ion studies have confirmed that the recycling of synaptic vesicles inv olves clathrin-mediated endocytosis. The rate of exocytosis would thus be limited by the capacity of the synaptic clathrin machinery unless vesicles could be drawn from existing pools. The mobilization of vesic les from the pool clustered at the release sites appears to provide a mechanism by which the rate of exocytosis can intermittently exceed th e rate of recycling. Perturbation of synapsins causes disruption of ve sicle clusters and impairment of synaptic transmission at high but not at low frequencies. Both clathrin-mediated recycling and mobilization of vesicles from the reserve pool are thus important in the replenish ment of synaptic vesicles. The efficacy of each mechanism appears to d iffer between synapses which operate with different patterns of activi ty.