INTRISIC NEUROMODULATION OF A SMALL NEURONAL NETWORK

Georgia State University, Atlanta GA

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Abstract

DESCRIPTION (provided by applicant): Neuromodulation, the neurochemical alteration of neuronal and synaptic properties, is important for motor pattern generation and behavioral plasticity, yet few studies have explored the dynamics of neuromodulatory signaling in neuronal circuits. The goals of this project are to understand how intracellular signals mediating neuromodulatory actions are dynamically integrated over time and how this contributes to the production and plasticity of a motor behavior. The system being studied is the central pattern generator (CPG) underlying the rhythmic escape swimming response of the gastropod mollusc, Tritonia diomedea. This model system is uniquely suited to address these issues because it contains identified neurons, intrinsic to the CPG circuit, that use serotonin (5-HT) to evoke neuromodulatory actions in other CPG neurons. The proposed experiments test the hypotheses that the dynamics of 2nd messenger signaling evoked by this "intrinsic neuromodulation" play a direct role in motor pattern production and that summation of 2nd messenger signals contributes to termination of the behavior and to its habituation. Aim I is to visualize the temporal dynamics of Ca 2+ and cAMP during motor pattern production. Aim 2 is to identify which second messengers mediate particular neuromodulatory actions of 5-HT and serotonergic neurons. Aim 3 is to test the behavioral roles of dynamic biochemical signaling during motor pattern generation and plasticity. The experimental methods include electrophysiological and optical recordings in situ and in primary cell culture. Real-time changes in Ca 2+ and cAMP levels are measured using confocal and multiphoton imaging of fluorescent indicators. Second messengers are manipulated both pharmacologically and in real time with rapid photolysis of caged compounds. The objective is to directly observe and perturb dynamic biochemical signals during the production of the motor behavior. These experiments will elucidate general principles of how neuromodulatory signals are temporally integrated over behaviorally relevant time scales, thereby uniting the operation of neuronal networks with intracellular biochemical signaling networks. Understanding the dynamics of neuromodulatory mechanisms underlying signaling by biogenic amines in a motor system is likely to have significance for diseases related to defects in aminergic signaling such as Parkinson's disease and Huntington's disease.