This exploratory grant will establish the research infrastructure to facilitate the creation of a Neuroscience Research Center for the training of minority Neuroscientist at a historically black institution. The research program is focused around the central unifying theme of circadian rhythms. We plan to study the molecular mechanisms that determine circadian signal generation by the circadian oscillator and the influence of the circadian oscillator on motor mechanisms and behavior. The overall program is composed of four interrelated projects. Dr. Moore's project 1 will address the molecular mechanisms that generate and maintain autogenic circadian activity of the suprachiasmatic nucleus of the hypothalamus (SCN). These studies are designed to isolate and characterize SCN specific gene products that constitute components of the endogenous circadian oscillator. Identification of components of the circadian signal transduction pathways will facilitate subsequent elucidation of the molecular mechanisms that regulate their gene expression or specific activation. Dr. Moore's project 1 addresses the mechanisms by which the SCN control the synthesis and secretion of melatonin by the pineal gland. This project will also address the effect of melatonin on the synthesis of dopamine. Dr. Patrickson's project is designed to study the neuroanatomical substrates involved in circadian locomotor activity. Preliminary data suggest that circadian signals generated by the SCN are transmitted to the motor system by efferent neuronal projections. These studies will identify the SCN efferent projections and termination site(s) communicating circadian signals within the motor system. The significance of this/these site(s) in restoration of circadian locomotor activity by SCN implants in SCN lesioned animals will be evaluated. In the project 3 by Dr. Whittaker we examine the electrophysiological mechanisms in the circadian control of motor function. There is evidence that the release of dopamine within the basal ganglia exhibits a circadian pattern. This may infer a similar pattern of basal ganglia function. This project will study the distribution of dopamine (DA) and excitatory amino acids (EAA) receptors in the rat substantia nigra and the effects of circadian signals on these receptors. In addition, the humoral effects of melatonin on DA and EAA modulatory mechanisms in the substantia nigra will be investigated in brain slices using conventional current-clamp of nigral neurons as well as whole cell patch-clamp techniques. In project 4 (Dr. Moore) the relationship between circadian rhythms and behavior will be addressed. A unique resident- intruder conflict paradigm will be investigated to explore the role of variation in light/dark cycle, exogenous melatonin administration, diazepam and dopaminergic agents on social behavior, locomotor activity, and circadian rhythms.
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