Circadian output mechanisms in nocturnal and diurnal animals

夜间和白天动物的昼夜节律输出机制

• 批准号: 10713602
• 负责人: JEFFREY R JONES
• 金额: $ 37.55万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713602
• 关键词: Address; African; Animals; Behavior; Behavioral; Biological; Brain; Cardiovascular Diseases; Chronobiology; Circadian Dysregulation; Circadian Rhythm Sleep Disorders; Communication; Curiosities; Disease; Etiology; Exhibits; Food; Foundations; Gene Expression; Genes; Goals; Health; Human; Investigation; Laboratory mice; Life Style; Light; Link; Machine Learning; Metabolic Diseases; Molecular; Mood Disorders; Mus; Neurons; Neurophysiology - biologic function; Outcome; Output; Partner in relationship; Periodicity; Physiological Processes; Predatory Behavior; Research; Rest; Signal Transduction; Symptoms; Time; circadian; circadian biology; circadian pacemaker; ex vivo imaging; genome editing; in vivo; molecular clock; multilevel analysis; novel; preference; programs; shift work; suprachiasmatic nucleus

Project Summary Animals have evolved circadian (near-24 h) rhythms to anticipate and adjust their behavior to daily opportunities and challenges such as mating, food availability, and predation. These behavioral rhythms are synchronized to the solar day by the central circadian pacemaker, the suprachiasmatic nucleus (SCN). SCN neurons exhibit daily rhythms in firing rate and clock gene expression that communicate circadian time to the rest of the brain and body. However, critically, we do not know how SCN signals interact with molecular and neuronal clocks in downstream neurons to generate circadian outputs. Our lab’s overarching goal is thus to understand how circadian input from the SCN is encoded by target neurons to ultimately generate diverse behavioral rhythms that peak at different times of day. To address this, over the next five years, our research program will focus on several interrelated but independent themes, including defining the “transfer function” for circadian output circuits, determining how molecular clocks in target neurons contribute to behavioral rhythmicity, and understanding how target neurons integrate diverse inputs to generate behavioral rhythms. We propose that endogenous rhythmicity in downstream neurons and daily input from SCN neurons are each required to drive appropriately timed circadian behavioral outputs. Here, we will use multi-level analysis at the molecular, circuit, and behavioral levels including targeted genomic editing of clock genes, in vivo and ex vivo imaging of rhythmic neurons, and machine learning analysis of behavior to dissect circadian output circuitry in two complementary species, the nocturnal laboratory mouse and the diurnal African striped mouse. Curiously, molecular and neuronal activity rhythms in the SCN peak at similar times in diurnal and nocturnal animals. How does an ostensibly identical SCN rhythm determine these dramatically different temporal niches? Our approach will allow us to address this and other long-standing questions in chronobiology by identifying both the mechanisms that temporally organize behaviors and the differences in molecular and neural function that decide an animal’s temporal niche preference. Identifying the genes, neurons, and circuits that regulate the timing of behavior in both laboratory mice and striped mice will also provide a novel framework for understanding the biological basis of chronotype in humans and the etiology of circadian rhythm sleep disorders. The discoveries we will make through our research program can generalize beyond circadian biology to reveal fundamental mechanisms linking genes and circuits to behavior.

项目概要 动物已经进化出昼夜节律（近 24 小时）来预测和调整其日常行为 这些行为节奏是机会和挑战，例如交配、食物供应和捕食。 通过中央昼夜节律起搏器视交叉上核（SCN）与太阳日同步。 神经元在放电率和时钟基因表达方面表现出每日节律，将昼夜节律时间传达给神经元 然而，重要的是，我们不知道 SCN 信号如何与分子和身体相互作用。 因此，我们实验室的首要目标是下游神经元中的神经元时钟产生昼夜节律输出。 了解来自 SCN 的昼夜节律输入如何由目标神经元编码以最终生成不同的 为了解决这个问题，我们在未来五年内进行了研究。 计划将重点关注几个相互关联但独立的主题，包括定义“传递函数” 昼夜节律输出电路，确定目标神经元中的分子钟如何影响行为 节律性，并了解目标神经元如何整合不同的输入以产生行为节律。 我们提出下游神经元的内源节律性和 SCN 神经元的日常输入分别是 在这里，我们将使用多层次分析来驱动适当的定时昼夜节律行为输出。 分子、电路和行为水平，包括体内和离体时钟基因的靶向基因组编辑 节律神经元成像，以及机器学习行为分析，以剖析昼夜节律输出电路 两个互补的物种，夜间活动的实验室小鼠和白天活动的非洲条纹小鼠。 昼夜动物的 SCN 峰值时间与分子和神经活动节律相似。 表面上相同的 SCN 节律是否决定了我们这些截然不同的时间生态位？ 该方法将使我们能够通过确定两者来解决这个问题以及时间生物学中其他长期存在的问题 暂时组织行为的机制以及分子和神经功能的差异 决定动物的时间生态位偏好识别调节的基因、神经元和电路。 实验室小鼠和条纹小鼠的行为时间也将为 了解人类睡眠时间型的生物学基础和昼夜节律睡眠的病因学 我们通过研究计划获得的发现可以推广到昼夜节律之外。 生物学揭示将基因和电路与行为联系起来的基本机制。