We analyzed the synaptic physiology of unc-13 mutants in the nematode
C. elegans. Mutants of unc-13 had normal nervous system architecture,
and the densities of synapses and postsynaptic receptors were normal at the
neuromuscular junction. However, the number of synaptic vesicles at neuromuscular
junctions was two- to threefold greater in unc-13 mutants than in wild-type
animals. Most importantly, evoked release at both GABAergic and cholinergic
synapses was almost absent in unc-13 null alleles, as determined by
whole-cell, 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 hyperosmotic
saline. These experiments support models in which UNC-13 mediates either fusion
of vesicles during exocytosis or priming of vesicles for fusion.
