Mechanisms Underlying Seasonal Adaptation of Daily Behaviors

日常行为季节性适应的机制

• 批准号: 9920226
• 负责人: ISAAC EDERY
• 金额: $ 33.91万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920226
• 关键词: 3' Untranslated Regions; Affect; Animal Model; Animals; Antibodies; Arousal; Behavior; Biochemical; Biological Models; Brain; CRISPR/Cas technology; Cell Culture Techniques; Complex; Cues; Diet; Disease; Drosophila genus; Drosophila melanogaster; Drowsiness; Eating; Equilibrium; Exhibits; Exposure to; Feeding behaviors; Foundations; Gene Expression; Genes; Genetic Transcription; Glucagon; Glucose; Glycogen; Health; Homologous Gene; Human; Hunger; Infection; Insulin; Insulin Signaling Pathway; Introns; Invertebrates; Juvenile Hormones; Lead; Life; Light; Link; Mammals; Mediating; Metabolic; Metabolic Pathway; Metabolic syndrome; Metabolism; Molecular; N-terminal; Narcolepsy; Neuropeptides; Non-Insulin-Dependent Diabetes Mellitus; Norepinephrine; Nutritional status; Octopamine; Pathway interactions; Pattern; Peptide Signal Sequences; Personal Satisfaction; Physiological; Proteins; RNA Interference; RNA Splicing; Reagent; Regulation; Research; Role; Seasons; Sensory; Signal Pathway; Signal Transduction; Sleep; Sleep Disorders; Sleep Wake Cycle; System; Temperature; Time; Tissues; Transgenic Organisms; Up-Regulation; Wakefulness; Work; adipokinetic hormone; base; circadian; circadian pacemaker; circadian regulation; feeding; fly; gene function; genome editing; hormone binding protein; hypocretin; insight; insulin signaling; insulin-like peptide; mRNA Expression; mutant; novel; programs; protein expression; response; sleep pattern; sleep quality; sleep regulation; spatiotemporal; warm temperature

Daily wake-sleep cycles are a pervasive feature of animal life, and disruptions in sleep are associated with numerous health related disorders in humans. The circadian timing system generally regulates the timing of wake and sleep to specific times in the day depending on whether an animal is diurnal or nocturnal. In addition to circadian regulation, daily wake-sleep patterns are governed by a complex balance between homeostatic sleep promoting pathways, arousal circuits, environmental signals (e.g., light and temperature) and internal state, such as nutritional status. In this proposal we will use Drosophila as a model system to understand how daily wake-sleep cycles adapt to seasonal changes in environmental conditions, with an emphasis on the relatively uncharacterized role of temperature. Temperature has been shown to have widespread effects on sleep in both Drosophila and humans. For example, many diurnal animals respond to warm temperatures by increasing daytime sleep or ‘siesta’, almost certainly an adaptive response to minimize exposure to heat. A major foundation for our proposal is based on our long-standing work showing that in D. melanogaster the temperature- dependent splicing of the 3'-terminal intron (called dmpi8) from the key circadian clock component termed period (per) is a prominent ‘thermosensor’ that adjusts the distribution of daily wake-sleep cycles, eliciting seasonably appropriate responses. For example, on warm days splicing of the dmpi8 intron is inefficient somehow leading to a longer midday siesta. In more recent findings we showed that the thermosensitive splicing of dmpi8 modulates the distribution of daily activity via a non-circadian mechanism that involves changes in sensory- mediated arousal. We will undertake a multi-faceted experimental strategy that includes biochemical, molecular, cell-culture and whole animal approaches to characterize this novel arousal/sleep circuit.

每天醒来-睡眠周期是动物生活中普遍存在的特征，睡眠中断与 人类中存在大量与健康相关的疾病。昼夜节律计时系统通常调节 根据动物是白天活动的还是夜间活动的，每天醒来和睡觉到特定的时间。此外 对于昼夜节律，每天的醒-睡模式是由动态平衡之间的复杂平衡控制的 促进睡眠的通路、唤醒电路、环境信号(例如，光和温度)和内部状态， 比如营养状况。在这项提案中，我们将使用果蝇作为模型系统来了解每天 觉醒-睡眠周期适应环境条件的季节性变化，重点是相对 温度所扮演的角色尚未确定。研究表明，温度对睡眠有广泛的影响。 果蝇和人类。例如，许多白天活动的动物对温暖的温度的反应是 白天睡眠或午睡，几乎可以肯定是一种适应性反应，以最大限度地减少暴露在高温下。一位少校 我们建议的基础是基于我们长期的研究表明，在黑腹蛇体内，温度- 3‘-末端内含子(称为dmpi8)从称为PERIOD的关键昼夜节律时钟成分中的依赖剪接 (PER)是一种显著的“温度传感器”，它可以调节日常觉醒-睡眠周期的分布，从而季节性地引发 适当的回应。例如，在温暖的日子里，dmpi8内含子的剪接在某种程度上是低效的 到更长的午睡时间。在最近的研究中，我们发现dmpi8的温敏性剪接 通过一种非昼夜机制调节日常活动的分布，这种机制涉及感官的变化- 中介的性唤醒。我们将采取多方面的实验战略，包括生化，分子， 细胞培养和全动物方法来描述这种新的唤醒/睡眠回路。