Neural circuitry and functional significance of extra-SCN pacemakers

SCN 外起搏器的神经回路和功能意义

• 批准号: 10427419
• 负责人: SHIN YAMAZAKI
• 金额: $ 38.54万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10427419
• 关键词: Anatomy; Area; Behavior; Behavioral; Body Temperature; Brain; Cell Nucleus; Chronic; Circadian Dysregulation; Circadian Rhythms; Coupled; Cre driver; Data; Diagnosis; Disabled Persons; Disease; Dissociation; Dopamine; Dopamine D1 Receptor; Dopamine Receptor; Dose; Drug Addiction; Exhibits; Exposure to; Feedback; Food; Food Intake Regulation; Goals; Health; Human; Hypothalamic structure; Impairment; Knockout Mice; Knowledge; Lead; Light; Location; LoxP-flanked allele; Mammals; Maps; Melatonin; Methamphetamine; Methodology; Microscopy; Modeling; Molecular; Motor Activity; Mus; Neurons; Organ; Organism; Output; Pacemakers; Palate; Patients; Periodicity; Peripheral; Persons; Phase; Physiological; Physiological Processes; Physiology; Process; Prosencephalon; Rewards; Risk; Rodent; Role; Running; Signal Transduction; Sleep; Sleeplessness; Slow-Wave Sleep; Stimulant; Stimulus; System; Technology; Tertiary Protein Structure; Testing; Time; Tissues; Transgenes; circadian; circadian pacemaker; feeding; human disease; insight; molecular imaging; nervous system disorder; neural circuit; neural network; novel; prevent; promoter; relating to nervous system; shift work; small hairpin RNA; suprachiasmatic nucleus; two-photon

Project Summary Circadian rhythms are fundamental to living organisms. The mammalian circadian system, which controls daily rhythms of behavior and physiology, is a multi-oscillatory system composed of a master pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) and many other oscillators in peripheral organs. However, the SCN is not the only pacemaker. When arousing stimuli are present, circadian behavior rhythms are observed even when circadian clocks in the SCN and peripheral tissues are disabled. The molecular mechanisms, anatomical loci, and functional significance of these extra-SCN pacemakers are not known. We have assembled molecular and imaging toolsets and technologies to identify the neural circuitry and physiological outputs of those extra-SCN pacemakers. The proposed studies will uncover the functional significance of the enigmatic extra-SCN circadian pacemakers in mammals. The discovery of the loci and physiological roles of the extra-SCN pacemakers will expand our understanding of the molecular and physiological processes of the circadian system. Importantly, our studies will investigate how the SCN and extra-SCN pacemakers interact to regulate feeding and sleep. Disruption of circadian rhythms and sleep by shiftwork and exposure to artificial light at night increases the risk of human diseases. In addition, sleep and circadian rhythms are impaired in several neurological disorders and in persons with drug addictions. Therefore, understanding how extra-SCN pacemakers control circadian rhythms will elucidate novel processes that could be manipulated to manage circadian disruption in humans.

项目摘要 昼夜节律是生命有机体的基础。哺乳动物的昼夜节律系统，它控制着日常生活 行为和生理的节律，是一个由一个主控起搏器组成的多振荡系统 下丘脑视交叉上核(SCN)和周围器官中的许多其他振荡器。然而， SCN并不是唯一的起搏器。当存在唤醒刺激时，观察到昼夜行为节律。 即使在SCN和周围组织中的生物钟被禁用时也是如此。分子机制， 这些SCN外起搏器的解剖位置和功能意义尚不清楚。我们有 组装分子和成像工具包和技术，以识别神经电路和生理 这些额外的SCN起搏器的输出。拟议的研究将揭示 哺乳动物中神秘的SCN外昼夜节律起搏器。 SCN外起搏器的基因座和生理作用的发现将扩大我们对它的认识 昼夜节律系统的分子和生理过程。重要的是，我们的研究将调查 SCN和Extra-SCN起搏器如何相互作用来调节进食和睡眠。昼夜节律紊乱 夜间轮班和暴露在人造灯光下的节奏和睡眠增加了人类疾病的风险。在……里面 此外，睡眠和昼夜节律在一些神经系统疾病和吸毒者中也会受到损害。 上瘾。因此，了解额外的SCN起搏器是如何控制昼夜节律的将有助于阐明 可以被操纵来管理人类昼夜节律紊乱的过程。