The suprachiasmatic nucleus (SCN) of the hypothalamus is the primary mammalian circadian pacemaker. The SCN receives retinal input through two pathways, the retinohypothalamic tract and the geniculohypothalamic tract (GHT). The GHT is an indirect pathway that includes the intergeniculate leaflet of the thalamus (IGL). One of the primary neurotransmitters of the GHT is neuropeptide Y (NPY). Although there is substantial evidence that NPY is involved in nonphotic entrainment during the subjective day, there is less research investigating the ability of NPY to modulate photic entrainment during the subjective night. The proposed research plan will test the hypothesis that NPY modulates photic phase shifts of activity rhythms and clock gene expression during the night. Specifically, NPY and NPY agonists are predicted to attenuate photic phase shifts, and NPY antagonists are predicted to potentiate photic phase shifts. The results of the proposed studies will provide important information regarding the entrainment process of circadian rhythms. Understanding the neurobiology of circadian rhythms may lead to new developments in the treatment of circadian disturbances associated with mental disorders such as depression, as well as dysonmias stemming from environmental changes such as shift work. ? ?