EXPERIENCE AND THE NEUROCHEMISTRY OF THE SYNAPSE

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The adaptability of the nervous system in response to changes in the environment is essential for the survival of an animal. With the exception of sensory nerves, which receive information about the environment directly, most nerve cells receive such information only indirectly, through changes in their synaptic and humoral inputs. It is the ability of neurons to change in response to changes in these inputs which ultimately produces many of the behavioral and physiological adaptations necessary for survival. The proposed research deals primarily with adaptive changes in two classes of proteins involved in synaptic function: the enzymes which regulate neurotransmitter biosynthesis and the proteins involved in neurotransmitter action. The approaches developed in studies on these ganglia will be used to study central nicotinic receptors. Previous work demonstrated that in addition to acetylcholine, preganglionic cervical sympathetic neurons release a second neurotransmitter. It also established that certain neuropeptides alter the activity of tyrosine hydroyxlase (TH), the enzyme which catalyzes the rate-limiting step in catecholamine biosynthesis. Our proposal has six specific aims: (1) to study the mechanisms involved in the acute regulation of TH activity by peptides of the secretin family, (2) to determine whether these peptides are neurotransmitters in the superior cervical ganglion, (3) to investigate whether cholinergic and peptidergic agonists stimulate TH activity in sympathetic nerve terminals and in adrenal chromaffin cells as they do in sympathetic neuron cell bodies, (4) to compare the stimulus properties required for the elicitation of an acute versus a long-term increase in TH activity, (5) to use toxin F (a snake venon neurotoxin) to study the regulation of ganglionic nicotinic receptors, and (6) to determine whether toxin F is also a useful ligand for characterizing neuronal nicotinic receptors in the central nervous system. These studies should elucidate mechanisms involved in the development of the nervous system and in its modification during adult life, both under normal conditions and in a variety of neurological and psychiatric disorders.