The long term goal of this research is to formulate general principles that explain how a defined set of neurons and muscles generates a range of complex behaviors, each of which displays unique parametric features. This research will use an integrated multidisciplinary approach in which the study of behavior and neuronal activity in intact animals is combined with experiments in semi-intact or simplified preparations. Analytical studies will combine biophysical, biochemical, molecular biological, and morphological techniques in order to obtain a set of tools that can be used under behaviorally relevant conditions. Thus, the plan is to perform a systems level analysis of the role that modulatory processes play in the generation of complex behaviors. In previous studies it has been shown that neuropeptides modify membrane properties and intracellular characteristics of their targets through interactions with each other and with primary classical transmitters. Proposed experiments will test the general hypothesis that peptide co-transmitters and primary transmitters are elements of parallel but distinct signaling pathways. Because peptide co-transmitters and primary transmitters are co-released this conceptualization implies that co-transmission may provide an elegant way to increase the flexibility of a system without the added complexity that would result from the incorporation of additional neurons. Many systems contain multiple modulatory peptides that are simultaneously co-released. In some areas these peptides exert qualitatively identical but quantitatively different effects. It will be determined whether mixtures of these types of peptides modulate a more extensive range of system parameters than single peptides. Finally, demands on elements of a system differ as the mode of behavior changes. It is suggested, therefore, that specific modes of behavior are associated with activity in specific populations of neurons and consequently with the release of specific combinations of peptide co-transmitters. This application places a special emphasis on the role of peptide co-transmitters. Despite the fact that these transmitters are ubiquitous in the nervous system, their functional role remains largely unknown. It is likely, therefore that clarification of the physiological role of neuropeptides in well defined circuits will provide insights into the role that these molecules play in normal and pathological forms of behavior.
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