Sleep Homeostasis, Plasticity and Memory

睡眠稳态、可塑性和记忆

• 批准号: 8434917
• 负责人: Ravi Allada
• 金额: $ 38.55万
• 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/8434917
• 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.

描述（由申请人提供）：不足的睡眠困扰着超过5000万美国人，导致认知功能和精神疾病的降低。在分子水平上，尚未很好地理解潜在的睡眠机制在睡眠障碍和精神疾病中破坏认知功能的问题。研究表明，精神疾病，睡眠体内平衡，突触可塑性与学习和记忆之间存在紧密联系。为了解决将这些神经过程联系起来的细胞和分子机制，我们一直在使用简单的模型生物，即果蝇果蝇。值得注意的是，果蝇表现出许多睡眠的核心特征。实际上，遗传分析表明，在果蝇和哺乳动物之间保守了许多参与调节睡眠水平的基因。作为了解果蝇的睡眠调节的研究的一部分，我们确定了特定神经基因座的作用，称为蘑菇体（MBS），在促进恢复性睡眠中。值得注意的是，MBS也是学习和记忆的核心。为了进一步了解与睡眠，唤醒和神经可塑性联系起来的神经和分子基础，我们建议进一步完善MB神经元在睡眠稳态中发挥特定作用。此外，我们将评估睡眠剥夺对MB依赖性学习和记忆以及MB突触的影响。我们还将研究学习与记忆基因与睡眠体内平衡之间的联系，包括关注它们在介导睡眠丧失对学习和记忆的影响中的作用。这些研究利用了果蝇系统的许多方面，包括睡眠，唤醒和记忆的保守机制，具有针对性的方式操纵的能力，可以在体内进行神经回路的功能，并易于操纵基因功能以阐明与睡眠，记忆，记忆，可塑性联系的机制。鉴于睡眠和记忆途径的遗传保护，这些研究可能会阐明睡眠不足的潜在机制及其与学习和记忆的关系以及人类的精神疾病。