Mediating effects of GRP on circadian rhythms

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DESCRIPTION (provided by applicant): Circadian rhythmicity in the primary mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus, is maintained by transcriptional and translational feedback loops involving the gene Per1. This gene is important for the entrainment or synchronization of circadian rhythms to the light-dark cycle. During photic stimulation, retinal terminals synapse onto neurons in the ventral SCN that contain gastrin releasing peptide (GRP). These neurons express Per1 in response to photic stimulation, while vasopressin- containing neurons in the dorsal region rhythmically express Per1. Given that GRP application to the SCN produces phase shifts, the current proposal will investigate whether photic entraining signals are mediated from retinorecipient cells to rhythm-generating clock cells by GRP. Using a Per1::GFP (green fluorescent protein) transgenic mouse, this proposal will characterize Per1-expressing cells in response to GRP application, and determine whether GRP receptor activation is sufficient and necessary to induce Per1 gene activity. This research investigating the role of SCN peptides in photic synchronization of circadian rhythms may lead to the development of treatments for circadian disruptions in mood and developmental disorders.