Photic and Nonphotic Interactions on Circadian Behavior

描述(申请人提供)：下丘脑的视交叉上核(SCN)是哺乳动物主要的昼夜节律起搏器。SCN通过视网膜下丘脑束和膝状下丘脑束(GHT)两条通路接受视网膜输入。GHT是一种间接通路，包括丘脑的膝间小叶(IGL)。神经肽Y(NPY)是GHT的主要神经递质之一。尽管有大量证据表明NPY参与了主观白天的非光性夹带，但对NPY在主观夜间调节光性夹带的能力的研究较少。拟议的研究计划将检验NPY调节夜间活动节奏和时钟基因表达的光相移的假设。具体地说，NPY和NPY激动剂预计会减弱光相移，NPY拮抗剂预计会增强光相移。拟议的研究结果将提供有关昼夜节律的夹带过程的重要信息。了解昼夜节律的神经生物学可能会导致在治疗与精神障碍相关的昼夜节律障碍方面取得新的进展，如抑郁症，以及由环境变化引起的失眠，如倒班工作。

DESCRIPTION (provided by applicant): 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.