Synaptic transmission is the process by which a signal is carried from one neuron to another across a synapse. This process begins when membrane depolarization of the presynaptic neuron stimulates the release of neurotransmitter into the synapse. Neurotransmitter then diffuses across the synaptic cleft and opens ligand-gated ion channels on the postsynaptic neuron. The integrity of synaptic transmission thus relies upon the regulated release of neurotransmitter from the synaptic cleft.

The synaptic vesicle cycle underlies the regulated release of neurotransmitter into the synapse. Synaptic vesicles are highly specialized organelles of the nerve terminal the store neurotransmitter. Proteins of the nerve terminal and the synaptic vesicle server to load synaptic vesicles with neurotransmitter, to position them for fusion with the membrane, to detect an increase in intracellular calcium due to membrane depolarization, to drive fusion of the vesicle with the membrane during depolarization, and to recover vesicles from the plasma membrane following fusion. For these reasons, worke aimed at elucidating a molecular mechanism of synaptic transmission has focused on defining the proteins of the presynaptic terminal that mediate the synaptic vesicle cycle.

The abundance of synaptic vesicles in nervous system tissue and the ease of their purification has led to the identification of a large number of synaptic-vesicle associated proteins. However, a precise molecular description of the mechanism of synaptic transmission has yet to be formulated, due in part to our limited understanding of the function of these proteins, and to an incomplete catalog of the proteins necessary for synaptic transmission. This thesis address these two difficulties by 1) characterizing the mutant phenotype of unc-26, the C. elegans ortholog of synaptojanin, demonstrating a role for the protein in synaptic vesicle recycling; and 2) cloneing the ric-1 gene which encode a novel multipass transmembrane protein that functions in cholinergic neurotransmission.