Sleep Homeostasis, Plasticity and Memory

睡眠稳态、可塑性和记忆

• 批准号: 8239497
• 负责人: Ravi Allada
• 金额: $ 40.16万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-08 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8239497
• 关键词: Accidents; Address; Adult; Affect; American; Animal Model; Area; Arousal; Behavior; Body part; Brain; Caffeine; Cell physiology; Cessation of life; Cognitive; Complex; Drosophila genus; Drosophila melanogaster; Exhibits; Genes; Genetic; Homeostasis; Human; Impaired cognition; Learning; Light; Link; Mammals; Mediating; Memory; Mental disorders; Modeling; Molecular; Movement; Mushroom Bodies; Neuronal Plasticity; Neurons; Organism; Output; Pathway interactions; Performance; Pharmaceutical Preparations; Phase; Play; Process; Proteins; Regulation; Resolution; Role; Series; Signal Pathway; Sleep; Sleep Deprivation; Sleep Disorders; Synapses; Synaptic plasticity; System; Testing; Training; base; cognitive function; experience; fly; gene function; genetic analysis; in vivo; memory process; neural circuit; neuromechanism; public health relevance; relating to nervous system; sensor; sensory stimulus; sleep regulation

DESCRIPTION (provided by applicant): Inadequate sleep afflicts over 50 million Americans, contributing to reduced cognitive function and psychiatric disorders. How underlying sleep mechanisms go awry in sleep disorders and mental illness to disrupt cognitive function is not well understood at the molecular level. Studies suggest an intimate link between mental illness, sleep homeostasis, synaptic plasticity, and learning and memory. To address the cellular and molecular mechanisms linking these neural processes, we have been using a simple model organism, the fruit fly Drosophila. Remarkably, the fruit fly exhibits many of the core features of sleep. In fact, genetic analysis suggests that many genes involved in regulating sleep levels are conserved between Drosophila and mammals. As part of our studies to understand sleep regulation in Drosophila, we identified a role for specific neural loci, termed the mushroom bodies (MBs), in promoting restorative sleep. Of note, the MBs are also central to learning and memory. To further understand the neural and molecular basis linking sleep, arousal, and neuroplasticity, we propose to further refine MB neurons playing specific roles in sleep homeostasis. In addition, we will assess the effects of sleep deprivation on MB-dependent learning and memory and MB synapses. We will also examine the link between learning and memory genes and sleep homeostasis, including a focus on their role in mediating the effects of sleep loss on learning and memory. These studies take advantage of many aspects of the Drosophila system, including conserved mechanisms of sleep, arousal, and memory, the ability to manipulate in a targeted manner the function of neural circuits in vivo and to easily manipulate gene function to elucidate mechanisms linking sleep, memory and plasticity. Given the genetic conservation of sleep and memory pathways, these studies may shed light on underlying mechanisms of disordered sleep and its relationship to learning and memory as well as mental illness in humans. PUBLIC HEALTH RELEVANCE: Inadequate sleep afflicts millions of Americans and contributes to mental illness. Here we use a simple model to elucidate the fundamental molecular and neural mechanisms linking sleep and memory.

描述（由申请人提供）：睡眠不足困扰着超过5000万美国人，导致认知功能下降和精神疾病。在分子水平上，睡眠障碍和精神疾病中潜在的睡眠机制是如何出错从而破坏认知功能的，还没有得到很好的理解。研究表明，精神疾病、睡眠稳态、突触可塑性和学习记忆之间有着密切的联系。为了解决连接这些神经过程的细胞和分子机制，我们一直在使用一种简单的模式生物，果蝇。值得注意的是，果蝇表现出许多睡眠的核心特征。事实上，基因分析表明，许多参与调节睡眠水平的基因在果蝇和哺乳动物之间是保守的。作为我们了解果蝇睡眠调节研究的一部分，我们确定了特定的神经位点，称为蘑菇体（mb），在促进恢复性睡眠中的作用。值得注意的是，mb也是学习和记忆的核心。为了进一步了解睡眠、觉醒和神经可塑性之间的神经和分子基础，我们建议进一步完善在睡眠稳态中发挥特定作用的MB神经元。此外，我们将评估睡眠剥夺对MB依赖性学习记忆和MB突触的影响。我们还将研究学习和记忆基因与睡眠稳态之间的联系，包括关注它们在调节睡眠缺失对学习和记忆的影响方面的作用。这些研究利用了果蝇系统的许多方面，包括睡眠、觉醒和记忆的保守机制，在体内以有针对性的方式操纵神经回路功能的能力，以及容易操纵基因功能来阐明连接睡眠、记忆和可塑性的机制。鉴于睡眠和记忆途径的遗传守恒，这些研究可能会揭示睡眠紊乱的潜在机制及其与人类学习和记忆以及精神疾病的关系。