Locomotor activity exhibits a circadian pattern in its expression. Strong experimental evidence exist demonstrating that the circadian entrainment of motor activity is controlled by the suprachiasmatic nucleus of the hypothalamus (SCN). The goal of this study is to elucidate the mechanisms by which the SCN entrains locomotor activity. The striatum, a component of the basal ganglia, is a principal integrative site for motor activity. The striatum, a component of the basal ganglia, is a principal integrative site for motor activity. Dopaminergic input is critical to the physiology of the striatum and the functional activity of the basal ganglia. Increases in the level of dopamine (DA) are associated with a concomitant increase in locomotor activity. Alternatively, reduction in DA levels results in akinesia as seen in Parkinson's disease. During normal activity, striatal DA levels fluctuate in a circadian pattern. We hypothesize that circadian entrainment of locomotor activity is effected by the temporal modulation of dopamine levels and/or the expression of dopamine receptors within the striatum by the SCN. To test this hypothesis we will first evaluate the relationship between the circadian fluctuations of striatal DA levels and the expression of locomotor activity by maintaining a constant DA level in the normal, or DA denervated animals (Aim 1). We will also investigate the temporal expression patterns of DA receptor subtypes during the circadian cycle utilizing in situ hybridization assays and pharmacologically assess their respective roles in the circadian expression of locomotor activity (Aim 2). Finally, utilizing electrophysiological techniques, we will determine if the circadian fluctuation of striatal DA levels can be correlated with the electrical activity of the nigrostriatal neurons within the substantia nigra pars compacta or intrinsic striatal mechanisms (Aim 3). The results from these studies will provide insight into mechanisms by which the SCN entrains locomotor activity and behavior.
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