UNC-13 is required for synaptic vesicle fusion in C-elegans

We analyzed the synaptic physiology of unc-13 mutants in the nematode C, el egans. Mutants of unc-13 had normal nervous system architecture, and the de nsities of synapses and postsynaptic receptors were normal at the neuromusc ular junction. However, the number of synaptic vesicles at neuromuscular ju nctions was two- to threefold greater in unc-13 mutants than in wild-type a nimals. Most importantly, evoked release at both GABAergic and cholinergic synapses was almost absent in unc-13 null alleles, as determined by whole-c ell, voltage-clamp techniques. Although mutant synapses had morphologically docked vesicles, these vesicles were not competent for release as assayed by spontaneous release in calcium-free solution or by the application of hy perosmotic saline. These experiments support models in which UNC-13 mediate s either fusion of vesicles during exocytosis or priming of vesicles for fu sion.