Integration of photic and nonphotic signaling in the circadian pacemaker

哺乳动物的生物钟在生理上驱动和维持24小时的节律，并整合了 信号转变为与环境一致的相变。这项建议的研究目标是 研究初级哺乳动物昼夜节律中这种整合下的神经肽通讯 起搏器，视交叉上核(SCN)。为了调查昼夜节律网络是如何 SCN解释相互冲突的相移刺激、实时时钟基因成像、晶状体成像和 将结合电生理端点来探索光和非光刺激的相互作用以及 使用一种独特的动物模型后神经生理学和分子节律的后续变化 (per1：：gfp)，允许检查活着的、表达perl的个体的神经生理属性。 细胞。初步数据表明，在SCN内，由胃泌素释放肽介导的光信号 (GRP)导致神经生理活动在早期和晚期持续增加。 夜间，尽管有不同的离子机制。这个项目的目标是研究如何 光神经化学信号(如GRP)与非光神经化学信号相互作用以调节 时钟细胞神经生理学。具体地说，我将使用PER1：：GFP和PER2：：Luc小鼠：(1)确定 光和非光同时携带刺激的位相依赖和传导机制，(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，以及(3)确定无光的神经生理和分子效应 神经肽Y(NPY)递质在昼夜节律周期中变化。拟议的研究计划将 阐明光和非光通路如何汇聚来调节生物钟基因和时钟细胞 最终决定相变的神经生理学。这些研究的结果具有一定的意义。

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