Photic Entrainment of Circadian Behaviors

描述（由申请人提供）：本项目将继续研究神经化学信号如何在下丘脑视交叉上核（SCN）内相互作用，以使昼夜节律与昼夜周期同步。由于昼夜节律计时系统的紊乱与各种精神疾病有关，因此了解昼夜节律的神经生物学应该会导致这些疾病的新治疗方法的发展。至少有三种不同的传入投射的SCN参与光夹带的昼夜节律。视网膜下丘脑束是从视网膜的直接投射，其对于对光刺激的夹带是必要且充分的。从中缝和膝状体间小叶到SCN的投射也影响光夹带。此外，有证据表明，这些预测可能介导的非光刺激的相移效果。该项目的长期目标是通过定义光和非光信息如何在SCN内进行通信和处理来定义昼夜节律夹带的神经化学基础。在接下来的四年中，我们将测试的工作假设，GABA内释放的SCN调制的昼夜节律起搏器的能力，在昼夜节律周期的不同阶段的相移。更具体地说，我们提出，在白天，GABA介导任何刺激产生的相移（例如，NPY或5-HT）通过其对时钟细胞的直接作用。在夜间，GABA介导任何刺激（NPY或5-HT）的能力，通过其对时钟细胞的直接作用来抑制光诱导的相移。此外，我们还将测试GABA调节两个时钟基因（即，Per 1和Per 2），已被假设为调节昼夜节律的相移。现有的证据表明，Per 1和Per 2 mRNA水平在白天通过相移刺激降低，在夜间通过光照增加。因此，我们建议，在白天或夜间释放的GABA将降低Per 1和Per 2 mRNA水平。

DESCRIPTION (provided by applicant): This project will continue to investigate how neurochemical signals interact within the suprachiasmatic nucleus of the hypothalamus (SCN) to synchronize circadian rhythms in behavior with the day-night cycle. Since disorders of the circadian timing system have been linked to a variety of mental illnesses, understanding the neurobiology of circadian rhythms should lead to the development of new treatments for these disorders. At least three different afferent projection of the SCN are involved in the photic entrainment of circadian rhythms. The retinohypothalamic tract is a direct projection from the retina that is necessary and sufficient for entrainment to photic stimuli. Projections from the raphe and the intergeniculate leaflet to the SCN also influence photic entrainment. In addition, there is evidence that these projections may mediate the phase shifting effects of nonphotic stimuli. The long-term goal of this project is to define the neurochemical basis of the entrainment of circadian rhythms by defining how photic and nonphotic information is communicated to and processed within the SCN. During the next four years we will test the working hypothesis that GABA released within the SCN modulates the capacity of the circadian pacemaker to phase shift at different phases of the circadian cycle. More specifically, we propose that during the day GABA mediates the phase shifts produced by any stimulus (e.g., NPY or 5-HT) by its direct actions on clock cells. During the night, GABA mediates the ability of any stimulus (NPY or 5-HT) to inhibit light-induced phase shifts by its direct action on clock cells. Further, we will also test the hypothesis that GABA regulates the mRNA levels of two clock genes (i.e., Per1 and Per2) that have been hypothesized to regulate phase shifts of circadian rhythms. Existing evidence indicates that Per1 and Per2 mRNA levels are reduced by phase shifting stimuli during the day and increased by light during the night. We therefore propose that GABA released during the day or during the night will reduce Per1 and Per2 mRNA levels.