Dr. Walrond describes an in depth study of the structure of the sites where neurotransmitter is released (active zones). He intends to determine the relationship between the organization of active zone components (active zone particles, synatic vesicles, and presynaptic densities) and the amount of transmitter released from synapses with diverse functions. Lobster (Homarus americanus) neuromuscular junctions provide a unique model system for these studies, since they contain synapses that release known amounts of neurotransmitter. The synapses will be identified in thin section and freeze-fracture views in the electron microscope. Dr. Walrond will examine three mechanisms that may regulate the amount of transmitter released: the number and density of large intramembrane particles aggregated at the transmitter release sites (active zone particles); the number of synaptic vesicles appropriately positioned to release transmitter (active zone vesicles); and the distance between the active zone vesicles, the active zone particles and the presynaptic density. These factors will be examined in three different preparations: in normal adult animals to correlate structure and function at mature, well-defined synapses; in developing synapses to correlate changes in active zone structure with changes in the amount of transmitter released during muscle growth; and in experimentally manipulated preparations to correlate long-term changes in the amount of transmitter released with changes in active zone structure accompanying altered patterns of neuronal activity. These studies will provide insights into the relationship between structure and function in one of the remaining puzzles of synaptic transmission: how functionally diverse synapses differentially control the amount of transmitter they release in response to a stereotyped signal, the action potential, and modulate the dynamic output of statically connected neural circuits.
