9418815 The long range goal of this research is to gain insight into mechanisms underlying the modulation of synaptic transmission. It is now clear that many neurons contain more than one transmitter and it is important to determine how multiple transmitters released from the terminals of single neurons interact on presynaptic and postsynaptic targets. Specifically, neuropeptide transmitters appear to commonly coexist along with conventional transmitters. The relatively simple nervous system of Aplysia has a number of advantages that make it particularly useful as a model system for these studies. One goal of this grant is to explore the manner in which neuropeptides that are released from motor neurons interact tio modulate the effectiveness of other transmitters released from the same neuron. A second goal is to investigate the effects of a biogenic amine, serotonin, released from purely modulatory neurons which have neuromuscular terminals. The neuropeptides and serotonin have been shown to be potent modulators of neuromuscular transmission. These studies have implications for vertebrate skeletal neuromuscular junctions where peptide cotransmitters have also been found. A third goal is to characterize the release of these peptide cotransmitters from identified neurons in primary culture. This highly reduced preparation permits detailed analyses of factors which regulate peptide release. Understanding fundamental neural processes such as the modulation of synaptic transmission at these neuromuscular synapses could provide a more general understanding of synapses which release multiple transmitters as well as have relevance to disorders of movement.
