Mediating effects of GRP on circadian rhythms

描述(申请人提供)：主要哺乳动物的昼夜节律起搏器，下丘脑的视交叉上核(SCN)，由涉及PER1基因的转录和翻译反馈环维持。这个基因对于昼夜节律与明暗周期的同步是很重要的。在光刺激过程中，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。这些神经元在光刺激下表达PER1，而背侧区域含有加压素的神经元有节律性地表达PER1。考虑到GRP应用于SCN会产生相移，目前的建议将调查光携带信号是否通过GRP从视网膜兴奋细胞传递到产生节律的时钟细胞。使用PER1：：GFP(绿色荧光蛋白)转基因小鼠，这项建议将表征表达PER1的细胞对GRP应用的响应，并确定GRP受体激活是否充分和必要地诱导PER1基因活性。这项研究探讨了SCN多肽在昼夜节律光同步中的作用，可能会导致开发治疗情绪和发育障碍的昼夜节律紊乱的方法。

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.