In this continuing project, the frog neuromuscular junction will be used to study the relation between synaptic competition and synaptic remodelling during synapse elimination. The central hypothesis is that competition is the force driving remodelling in both developing and adult synapses. The experiments will employ new methods for in vivo observation of neuromuscular junctions as well as detailed electrophysiological studies of morphologically identified junctions. The first specific aim is to make repeated, in vivo observations of synapse elimination and remodelling in reinnervated junctions. Histology suggests that motor nerve terminals remain highly dynamic long after regeneration is complete. Physiology reveals no net change in polyneuronal innervation, however.
The second aim i s to correlate the tendency of terminals to persist or retract during synapse elimination with their physiological properties. Reinnervated junctions will be observed in vivo. When synapse elimination begins, muscles will be removed and electrophysiology used to determine the functional properties of identified nerve terminal branches.
The third aim i s to determine the morphological and physiological correlates of synaptic competition during a different form of synapse elimination. Using a preparation in which muscle fibers are innervated at two distant junctional sites, comparisons will be made between fibers where the two sites are innervated by the same or different motoneurons. These experiments may reveal whether plasticity at neuromuscular junctions conforms to Hebbian principles. Neuromuscular junctions are the best understood of all chemical synapses. Although they are certainly different from brain synapses, it is highly likely that cellular mechanisms of plasticity discovered at neuromuscular junctions will have wide applicability. A thorough understanding of synaptic plasticity is essential, for such processes probably underlie learning and memory and determine the ability of the nervous system to recover from injury or disease.
