The SCN and Circadian Activity in the VTA

University Of Pennsylvania, Philadelphia PA

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Abstract

DESCRIPTION (provided by applicant): The suprachiasmatic nucleus (SCN) is a circadian pacemaker that synchronizes a number of vital physiological and behavioral processes. Although a great deal of research has focused on input pathways to the SCN and on the central clock itself, relatively little is known about SCN output signaling pathways. Ventral tegmental area (VTA) dopamine (DA) neurons have been extensively studied and play an important role in reward and reinforcement. However, possible circadian influences on VTA neurons have received little attention, in part because the SCN does not directly project to the VTA. Preliminary studies in our lab indicate that the VTA receives indirect projections from the SCN, and exhibits a circadian rhythm in impulse activity. There is an increase in the number of spontaneously active VTA DA neurons with overall increases in DA neuron firing irregularity during the active (dark) period as compared to the rest (light) period. Furthermore, a novel population of neurons with altered firing rates and pharmacological profile has been recorded, and seem to only be present during the active (dark) period. These findings indicate that substantial circadian regulation of VTA DA impulse activity may exist. It is therefore hypothesized that the SCN, through indirect connections with the VTA, influences the activity of VTA neurons in a circadian manner. Experiments using a trans-synaptic tracer will be used to specify an SCN-VTA circuit. In addition, the firing characteristics of VTA neurons will be investigated through the circadian cycle. Lastly, possible mechanisms underlying altered characteristics of the VTA during the circadian cycle will be investigated. Characterization of VTA circadian activity and its relation to the SCN will provide insights into how the SCN regulates complex behavioral processes.