Role of the ipRGC Circadian Clock in Visual Perception

ipRGC 生物钟在视觉感知中的作用

• 批准号: 10781913
• 负责人: Kayla C Miguel
• 金额: $ 4.35万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10781913
• 关键词: ARNTL gene; Affect; Animals; Attenuated; Automobile Driving; Awareness; Behavior; Behavioral; Behavioral Mechanisms; Biological Process; Biological Rhythm; Body Temperature; Cell physiology; Cells; Circadian Dysregulation; Circadian Rhythms; Clock protein; Contrast Sensitivity; Darkness; Data; Dopamine Receptor; Eating; Electrophysiology (science); Environment; Esthesia; Feedback; Foundations; Gene Expression; Genes; Genetic; Genetic Transcription; Goals; Health; Hormones; Hour; Human; Image; Individual; Intrinsic drive; Kinetics; Knock-out; Light; Lighting; Link; Measures; Modeling; Molecular; Mus; Organism; Outcome; Pacemakers; Periodicity; Physiology; Play; Process; Proteins; Pupil light reflex; Reflex control; Retina; Retinal Ganglion Cells; Role; Signal Transduction; Sleep Wake Cycle; Stimulus; Study models; Synapses; Techniques; Testing; Time; Tissues; Vertebrate Photoreceptors; Vision; Visual; Visual Perception; behavior influence; cell behavior; cell type; circadian; circadian pacemaker; environmental change; experimental study; insight; mRNA Expression; melanopsin; molecular clock; response; retinal neuron; tool; visual information; visual stimulus

PROJECT SUMMARY Circadian rhythms are biological changes that act over the course of the 24 hour day to allow animals to anticipate daily changes to their environment. These rhythms control many aspects of an animal’s physiology and behavior crucial for survival, including sleep/wake cycles, timing of food intake, body temperature, and hormone release, and their disruption leads to a variety of negative health outcomes. Circadian rhythms are set by molecular “clocks” contained within single cells in nearly every tissue of the body and are synchronized by the central pacemaker within the SCN to coordinate the timing of physiology and behavior across the day. Despite the huge number of biological processes under circadian control and increased awareness of the negative impacts of circadian disruption on human health, little is understood about how molecular clocks act within single cells throughout the body to control their function over the course of the day. One of the most predictable daily environmental changes is the light/dark cycle, which changes over several orders of magnitude from midday to midnight. Retinal neurons, which must anticipate and encode visual stimuli over this range, contain their own molecular clocks, and multiple visual behaviors are known to be under circadian control. The goal of this project is to use the retina as a model to understand how molecular clocks control cellular function to ultimately influence behavior. Contrast sensitivity and the pupillary light reflex (PLR) are two behaviors that are under circadian control. Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are major contributors to both of these behaviors and contain molecular clocks that oscillate throughout the day. Moreover, these cells can be manipulated with multiple genetic tools, making ipRGCs an excellent model for studying the impact of the molecular clocks of single cells to cell signaling and behavior. In Aim 1 we will determine whether the molecular clock of ipRGCs is necessary for proper PLR and contrast sensitivity. In Aim 2 we will determine how ipRGC cellular function is impacted by disruption of the molecular clock in ipRGCs. Collectively these results will provide insight into the impact of molecular clocks within single cells on cellular signaling and behavior.

项目摘要 昼夜节律是在24小时内起作用的生物学变化，以允许动物 预期每日对环境的变化。这些节奏控制着动物生理的许多方面 对于生存至关重要的行为，包括睡眠/唤醒周期，食物摄入时间，体温和 释放马内（Horseone）及其破坏会导致各种负面的健康结果。昼夜节律是 由分子“时钟”设置在人体几乎每个组织中的单个细胞中 由SCN中的中央起搏器由全天的生理和行为时间协调。 尽管在昼夜节律下进行了大量的生物过程，并提高了对 昼夜节律破坏对人类健康的负面影响，关于分子钟的行为几乎没有理解 在整个身体的单个细胞中，可以在一天中控制其功能。 最可预测的每日环境变化之一是光/黑暗周期，它在几个 从中午到午夜的数量级。视网膜神经元，必须预测和编码视觉刺激 在此范围内，包含自己的分子时钟，已知多种视觉行为已在 昼夜节律。该项目的目的是将视网膜作为模型来了解分子时钟 控制细胞功能以最终影响行为。 对比灵敏度和瞳孔光反射（PLR）是昼夜节律控制的两种行为。 表达黑素的，本质上光敏性的视网膜神经节细胞（IPRGC）是主要贡献者 这两种行为都包含整天振荡的分子钟。而且，这些细胞 可以用多种遗传工具来操纵，使IPRGC成为研究的绝佳模型 单细胞的分子钟到细胞信号传导和行为。在AIM 1中，我们将确定是否 IPRGC的分子时钟对于适当的PLR和对比度灵敏度是必需的。在AIM 2中，我们将确定 IPRGC细胞功能如何受到IPRGC分子时钟的破坏的影响。集体这些 结果将提供有关单个细胞中分子钟对细胞信号传导和 行为。