Mediating effects of GRP on circadian rhythms

描述（由申请人提供）：哺乳动物主要昼夜节律起搏器（下丘脑视交叉上核（SCN））的昼夜节律性由涉及基因Per1的转录和翻译反馈环维持。该基因对于昼夜节律与明暗周期的同步或同步很重要。在光刺激期间，视网膜终末与腹侧SCN中含有胃泌素释放肽（GRP）的神经元突触。这些神经元对光刺激的反应是表达Per1，而背侧区的含加压素的神经元有节奏地表达Per1。鉴于GRP应用于SCN产生相移，目前的建议将调查是否光夹带信号介导的视网膜受体细胞的节奏产生时钟细胞的GRP。使用Per1：：GFP（绿色荧光蛋白）转基因小鼠，该提案将表征Per1表达细胞对GRP应用的反应，并确定GRP受体激活是否足以诱导Per1基因活性。这项研究调查SCN肽在昼夜节律的光同步中的作用，可能会导致情绪和发育障碍中昼夜节律中断的治疗方法的发展。

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.