to neurexins, damaging vesicles and causing massive release of neurotransmitters. Vesicle pools Vesicles in the nerve terminal are grouped into three pools: the readily releasable pool, the recycling pool, and the reserve pool. These pools are distinguished by their function and position in the nerve terminal. The readily releasable pool are docked to the cell membrane, making these the first group of vesicles to be released on stimulation. The readily releasable pool is small and is quickly exhausted. The recycling pool is proximate to the cell membrane, and tend to be cycled at moderate stimulation, so that the rate of vesicle release is the same as, or lower than, the rate of vesicle formation. This pool is larger than the readily releasable pool, but it takes longer to become mobilised. The reserve pool contains vesicles that are not released under normal conditions. This reserve pool can be quite large (~50%) in neurons grown on a glass substrate, but is very small or absent at mature synapses in intact brain tissue. Physiology The synaptic vesicle cycle The events of the synaptic vesicle cycle can be divided into a few key steps: 1. Trafficking to the synapse Synaptic vesicle components are initially trafficked to the synapse using members of the kinesin motor family. In C. elegans the major motor for synaptic vesicles is UNC-104. There is also evidence that other proteins such as UNC-16/Sunday Driver regulate the use of motors for transport of synaptic vesicles. 2. Transmitter loading Once at the synapse, synaptic vesicles are loaded with a neurotransmitter. Loading of transmitter is an active process requiring a neurotransmitter transporter and a proton pump ATPase that provides an electrochemical gradient. These transporters are selective for different classes of transmitters. Characterization of unc-17 and unc-47, which encode the vesicular acetylcholine transporter and vesicular GABA transporter have been described to date. 3. Docking The loaded synaptic vesicles must dock near release sites, however docking is a step of the cycle that we know little about. Many proteins on synaptic vesicles and at release sites have been identified, however none of the identified protein interactions between the vesicle proteins and release site proteins can account for the docking phase of the cycle. Mutants in rab-3 and munc-18 alter vesicle docking or vesicle organization at release sites, but they do not completely disrupt docking. SNARE proteins, now also appear to be involved in the docking step