The long term goals of the proposed study are to understand how particular structural elements of the neuromuscular junction work - what roles they may play in synaptic transmission. The strategy of the immediate aims is to make systematic and quantitative structure-function correlations under situations in which the junctions are undergoing some kind of change or are functionally different. These comparisons are between different stages of developing junctions or degenerating junctions, junctions of a similar type but different function such as slow and fast excitatory neuromuscular junctions, or junctions under different levels of use at the moment of fixation. The method is to determine the level of performance of a population of neuromuscular junctions formed by one axon using electrophysiological techniques, and then to fix the muscle and examine the structure of the junctions with freeze-fracture, thin section and scanning electron microscopy. The structures to be examined include the length and particle composition of the active zone as seen in freeze-fracture, and the area occupied by, and the density of, the particles that are associated with the receptors in the postsynaptic membrane specialization. By combining the three ultrastructural techniques a quantitative evaluation of nerve terminal length, shape, number of active zones, and size and density of synaptic vesicles, can be obtained. The results allow us to make correlations between the presence or absence of a structural element and synaptic transmission. The results also describe in a more precise way the processes of synapse development and degeneration at a cellular level. We are also concerned with the possible roles of a group of neurosecretory axons which may modulate muscle physiology, neuro muscular junction activity or both during development and degeneration. The model for degeneration that has been selected, where a larval neuromuscular junction and the muscle degenerate prior to metamorphosis, may be closer to the etiology of disease states than that of nerve transection which is more commonly used.
