Integration of photic and nonphotic signaling in the circadian pacemaker

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The mammalian circadian clock drives and maintains 24-h rhythms In physiology and integrates multiple signals Into a phase change consistent with the environment. The research goal of this proposal is to investigate neuropeptide communication underiying this integration within the primary, mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). In order to investigate how the circadian network within the SCN Interprets conflicting phase shifting stimuli, real-time clock gene Imaging, phannacoioglcal and electrophysiological endpoints will be combined to explore the interaction of photic and nonphotic stimuli and the subsequent changes In neurophysiology and molecular rhythms using a unique animal model (Per1::GFP) that allows examination of neurophysiological properties of individual, living, Perl-expressing cells. Preliminary data suggest that within the SCN, photic signaling mediated by gastrin-releasing peptide (GRP) results In a persistent Increase In neurophysiological activity during the early and late phases of the night, although there are different underiying Ionic mechanisms. The goal of this project is to examine how photic neurochemical signaling (such as GRP) interacts with nonphotic neurochemical signaling to modulate clock cell neurophysiology. Speciflcally, I will use Per1::GFP and PER2::LUC mice to: (1) determine the phase dependence and transduction mechanisms for concurrent photic and nonphotic entraining stimuli, (2) investigate the neural circuitry and neurophysiology associated with GRP-mediated photic transduction during the day, and (3) determine whether the neurophysiological and molecular effects of the nonphotic transmitter, neuropeptide Y (NPY), vary across the circadian cycie. The proposed research plan will elucidate how photic and nonphotic pathways converge to regulate circadian clock genes and clock cell neurophysiology that ultimately determines the phase change. The results of these studies have Implications