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: 10252918
• 负责人: SHIN YAMAZAKI
• 金额: $ 38.52万
• 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/10252918
• 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; 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 昼夜节律是生物体的基础。哺乳动物的昼夜节律系统， 行为和生理节律，是一个多振荡系统，由主起搏器组成， 下丘脑视交叉上核（SCN）和许多其他周围器官的振荡器。但 SCN不是唯一的起搏器。当唤醒刺激存在时，观察到昼夜行为节律 即使当SCN和外周组织中的生物钟被禁用时。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集和技术，以识别神经回路和生理 这些额外SCN起搏器的输出。拟议的研究将揭示的功能意义， 哺乳动物中神秘的SCN外昼夜节律起搏器。 SCN外起搏器的定位和生理作用的发现将扩大我们的理解 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和额外SCN起搏器如何相互作用以调节进食和睡眠。昼夜节律紊乱 轮班工作和夜间暴露在人造光下会增加人类疾病的风险。在 此外，睡眠和昼夜节律在几种神经系统疾病和药物滥用者中受损。 上瘾因此，了解额外的SCN起搏器如何控制昼夜节律将阐明新的 这些过程可以被操纵来管理人类的昼夜节律紊乱。