Integration of photic and nonphotic signaling in the circadian pacemaker

哺乳动物的生物钟驱动并维持生理学上的24小时节律， 信号转变成与环境相一致的相变。本提案的研究目标是 研究神经肽通讯在这种整合的基础上，在初级，哺乳动物的昼夜节律 起搏器，视交叉上核（SCN）。为了研究昼夜节律网络是如何在 SCN解释冲突的相移刺激，实时时钟基因成像，药理学和 将结合电生理终点来探索光刺激和非光刺激的相互作用， 随后的神经生理学和分子节律的变化， (Per1：：GFP），其允许检查个体的、活的、表达Perl的 细胞初步数据表明，在SCN内，由胃泌素释放肽介导的光信号传导 (GRP)结果在神经生理活动的早期和晚期持续增加， 夜晚，虽然有不同的离子机制。这个项目的目标是研究如何 光神经化学信号传导（如GRP）与非光神经化学信号传导相互作用， 时钟细胞神经生理学特别地，我将使用Per1：：GFP和PER2：：LUC小鼠：（1）确定 光和非光共时夹带刺激的相位依赖和转导机制，（2） 研究与GRP介导的光传导相关的神经回路和神经生理学 在白天，和（3）确定是否神经生理和分子效应的非光的 神经肽Y（neuropeptide Y，NPY）是一种重要的神经递质。拟议的研究计划将 阐明光和非光途径如何会聚以调节生物钟基因和生物钟细胞 最终决定相变的神经生理学。这些研究的结果具有启示意义

The mammalian circadian clock drives and maintains 24-h rhythms In physiology and integrates multiple signals Into a phase change consistent with the environment. The research goal of this proposal is to investigate neuropeptide communication underiying this integration within the primary, mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). In order to investigate how the circadian network within the SCN Interprets conflicting phase shifting stimuli, real-time clock gene Imaging, phannacoioglcal and electrophysiological endpoints will be combined to explore the interaction of photic and nonphotic stimuli and the subsequent changes In neurophysiology and molecular rhythms using a unique animal model (Per1::GFP) that allows examination of neurophysiological properties of individual, living, Perl-expressing cells. Preliminary data suggest that within the SCN, photic signaling mediated by gastrin-releasing peptide (GRP) results In a persistent Increase In neurophysiological activity during the early and late phases of the night, although there are different underiying Ionic mechanisms. The goal of this project is to examine how photic neurochemical signaling (such as GRP) interacts with nonphotic neurochemical signaling to modulate clock cell neurophysiology. Speciflcally, I will use Per1::GFP and PER2::LUC mice to: (1) determine the phase dependence and transduction mechanisms for concurrent photic and nonphotic entraining stimuli, (2) investigate the neural circuitry and neurophysiology associated with GRP-mediated photic transduction during the day, and (3) determine whether the neurophysiological and molecular effects of the nonphotic transmitter, neuropeptide Y (NPY), vary across the circadian cycie. The proposed research plan will elucidate how photic and nonphotic pathways converge to regulate circadian clock genes and clock cell neurophysiology that ultimately determines the phase change. The results of these studies have Implications