Integration of photic and nonphotic signaling in the circadian pacemaker

昼夜节律起搏器中光信号和非光信号的集成

• 批准号: 7897077
• 负责人: Karen L Gamble
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7897077
• 关键词: Address; Affect; Animal Model; Automobile Driving; Award; Bombesin Receptor; Brain; Cells; Circadian Dysregulation; Circadian Rhythms; Communication; Conflict (Psychology); Data; Dependence; Electrophysiology (science); Environment; Exercise; GTP-Binding Proteins; Gastrin releasing peptide; Gene Expression Regulation; Genes; Glutamates; Goals; Image; In Vitro; Indium; Individual; Jet Lag Syndrome; Life; Light; Long-Term Depression; Mediating; Mentors; Modality; Molecular; Moods; Mus; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neurons; Neuropeptides; Pathway interactions; Pharmacology; Phase; Physiology; Property; Receptor Activation; Reporter; Research; Research Proposals; Signal Pathway; Signal Transduction; Slice; Stimulus; Stress; Testing; Time; Training; attenuation; base; circadian pacemaker; developmental disease; inward rectifier potassium channel; neural circuit; neurochemistry; neuropeptide Y; neurophysiology; phase change; relating to nervous system; shift work; suprachiasmatic nucleus; therapy development; voltage clamp

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

哺乳动物的生物钟驱动并维持24小时的生理节律，并整合了多种生物钟 信号转变为与环境一致的相变。本提案的研究目标是 研究在初级哺乳动物昼夜节律中这种整合的神经肽通讯 起搏器，视交叉上核（SCN）。为了研究体内的昼夜节律网络如何 SCN 解释冲突的相移刺激、实时时钟基因成像、药物和 将结合电生理学终点来探索光刺激和非光刺激的相互作用 使用独特的动物模型观察神经生理学和分子节律的后续变化 (Per1::GFP) 允许检查个体、活体、表达 Perl 的神经生理学特性 细胞。初步数据表明，在 SCN 内，由胃泌素释放肽介导的光信号传导 (GRP) 导致早期和晚期神经生理活动持续增加 晚上，尽管存在不同的底层离子机制。该项目的目标是研究如何 光神经化学信号传导（例如 GRP）与非光神经化学信号传导相互作用以调节 时钟细胞神经生理学。具体来说，我将使用 Per1::GFP 和 PER2::LUC 小鼠来： (1) 确定 并发光和非光夹带刺激的相位依赖性和转导机制，(2) 研究与 GRP 介导的光传导相关的神经回路和神经生理学 白天，（3）确定非光的神经生理学和分子效应是否 递质神经肽 Y (NPY) 在整个昼夜节律中变化。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。这些研究结果具有重要意义