Generation of Retinal Signals for Circadian Entrainment

产生昼夜节律的视网膜信号

• 批准号: 7237956
• 负责人: RONALD Lane BROWN
• 金额: $ 30.42万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-09 至 2007-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7237956
• 关键词: Alzheimer' s Disease; Behavior; Biochemical; Biochemistry; Biological Clocks; Blood Pressure; Body Temperature; Brain; Cations; Cells; Circadian Rhythms; Class; Cues; Daily; Depth; Detection; Disease; Employee Strikes; Exhibits; Family; Fire - disasters; Foundations; G-Protein Signaling Pathway; GTP-Binding Proteins; Generations; Goals; Grant; Housing; Human; Immunohistochemistry; Intervention; Intrinsic drive; Ion Channel; Jet Lag Syndrome; Light; Mammals; Mediating; Methods; Molecular; Neural Pathways; Neurons; Organism; Output; Patch-Clamp Techniques; Patients; Pattern; Performance; Photoreceptors; Physiology; Pigments; Plants; Play; Principal Investigator; Process; Property; Psyche structure; Range; Research; Retina; Retinal; Retinal Ganglion Cells; Role; Shapes; Shift-Work Sleep Disorder; Signal Pathway; Signal Transduction; Signaling Molecule; Sleep; Solutions; Synapses; System; Testing; Time; Transducin; Vertebrate Photoreceptors; Vision; Wakefulness; base; circadian pacemaker; day; design; improved; insight; interdisciplinary approach; light entrainment; melanopsin; member; nervous system disorder; novel; programs; research study; response; shift work; suprachiasmatic nucleus; tissue/cell culture; voltage

DESCRIPTION (provided by applicant): Many aspects of behavior and physiology, such as sleeping and wakefulness, blood pressure, and body temperature exhibit daily oscillations known as circadian rhythms. Disturbances in these circadian rhythms are responsible for the debilitating effects of jet lag, shift work and the sleep disorders seen in patients suffering from Alzheimer's disease. Circadian rhythms are driven by an intrinsic biological clock found in organisms ranging from plants to humans. In mammals, this biological clock is housed deep within the brain in two small clusters of cells called the suprachiasmatic nuclei (SCN). These intrinsic circadian rhythms are synchronized to the daily environmental cycle of day and night by the process of photoentrainment, which uses light information to reset the biological clock. In mammals, the neuronal signal for photoentrainment arises from a small subset of retinal ganglion cells (RGCs) that send a direct projection to the SCN. Surprisingly, the retinal signals that give rise to vision may be quite different from those responsible for circadian entrainment. Although retinal input is required for photoentrainment, traditional photoreceptors are not required. The solution to this apparent paradox may lie in the recent discovery that RGCs that project to the SCN express a novel photopigment, melanopsin, and can generate an intrinsic light response in the absence of photoreceptor-driven synaptic input. To date, little is known about the physiology of the RGCs that generate the retinal output to the circadian system. In this grant, we propose to use a multidisciplinary approach to study how these cells generate the retinal signals that produce photoentrainment. Specifically, we will determine 1) the signaling properties of melanopsin, the photopigment of the circadian system; 2) what intracellular signaling pathway generates the intrinsic response to light; and 3) the ion channel that mediates the intrinsic light response. This research will provide a foundation for improved treatment of circadian disorders that are often associated with neurological disorders, and are responsible for the debilitating effects of jet lag and shift work.

描述（由申请人提供）：行为和生理的许多方面，如睡眠和清醒，血压和体温表现出每天的振荡，称为昼夜节律。这些昼夜节律的紊乱会导致时差反应、轮班工作和阿尔茨海默氏症患者的睡眠障碍。昼夜节律是由内在的生物钟驱动的，从植物到人类都存在。在哺乳动物中，生物钟被安置在大脑深处的两个被称为视交叉上核（SCN）的小细胞群中。这些内在的昼夜节律通过光夹带过程与昼夜的日常环境循环同步，光夹带过程利用光信息来重置生物钟。