Molecular mechanisms of vesicle exocytosis, endocytosis and membrane trafficking in neurons. We are interested in understanding basic mechanisms of vesicle trafficking, especially at the synapse, where synaptic vesicle exocytosis and endocytosis occur with high speed and fidelity. We have described many of the protein components involved in clathrin-mediated vesicle retrieval in the synapse. We are now describing other faster endocytic pathways that operate in parallel with the slower clathrin-mediated retrieval pathway. We have recently discovered how vesicle exocytosis is so finely tuned to calcium entry and this in turn points to similar basic underlying mechanisms of control that are likely to operate in all vesicle fusion events. We would like to further understand the control points for post synaptic vesicle trafficking and are currently investigating the function of oligophrenin, mutations in which give rise to mental retardation.