MECHANISMS OF CENTRAL PATTERN GENERATION IN GANGLIA

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This proposal is to study the mechanisms by which central neural activity is modulated by neuropeptides. We will use a small model system, the stomatogastric ganglion of the lobster and the peptides CCK and proctolin to link chemically induced behavioral modifications with neuronal activity. CCK has hormonal-like actions in mammals -- acting on the brain to help terminate feeding (satiety hormone) and also appears to induce a general malaise in rats. There is evidence now that CCK has effects on both morphine and dopamine receptors. Its action as a satiety hormone has implicated CCK in such severe eating disorders as anorexia nervosa. Since CCK has been localized to CNS neurons it may have additional sites of action within the brain, i.e. more localized actions. Proctolin is a small pentapeptide which has also been found in the mammalian brain but its behavioral activity is as yet unknown. Proctolin and a CCK-like peptide have been found in the stomatogastric system. The stomatogastric networks are ideal for studying the effects of peptides because the thirty neurons in this system are identified and the neural circuits they form have been well described. Although peptides are known to have important behavioral effects, little is known about their actual mechanisms of action at the circuit and cellular level. The use of model systems enables us to study peptide action at this level. This project will link behavior with peptide action by quantifying the behavior in vivo by making simultaneous measurements of movements and CNS output -- either EMG or nerve recordings. We will compare spontaneous behavior with behavior induced by the systemic injection of proctolin and CCK. We will explore the roles of endogenous proctolin and a CCK-like peptide in the generation of gastric mill activity in vivo. These same substances will be bath-applied to the in vitro preparations. The sites of action will be determined by deleting cells from the network using a cell-killing technique to isolate single neurons and synapses. We will compare the modulated motor patterns in vitro to those seen in vivo and determine which neurons and synapses in the circuits are responsible for the changes.