Local Sleep Regulation and Brain Plasticity

局部睡眠调节和大脑可塑性

• 批准号: 7387401
• 负责人: GIULIO TONONI
• 金额: $ 32.95万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7387401
• 关键词: Affect; Animal Model; Animals; Area; Behavior; Biological; Biological Process; Brain; Brain region; Cerebral cortex; Cognition; Computer Simulation; Computers; Condition; Contralateral; Deafferentation procedure; Deterioration; Disease; Elbow; Electroencephalogram; Electroencephalography; Evoked Potentials; Frequencies; Genetic; Goals; Health; Homeostasis; Human; Immobilization; Impairment; Investigation; Joints; Laboratories; Lead; Learning; Left; Life; Limb structure; Localized; Location; Magnetic Resonance Imaging; Magnetism; Mammals; Mental Depression; Mental disorders; Methods; Mission; Molecular; Moods; Motor; Movement; National Institute of Mental Health; Neurobiology; Neurologic; Neurons; Organ; Orthopedics; Parietal; Parietal Lobe; Performance; Plastics; Play; Prefrontal Cortex; Procedures; Process; REM Sleep; Records; Regulation; Research; Research Personnel; Role; Rotation; Series; Shoulder; Sleep; Sleep Deprivation; Sleep Disorders; Slow-Wave Sleep; Somatosensory Evoked Potentials; Suggestion; Synapses; Tablets; Testing; Therapeutic; Upper arm; Wakefulness; Work; Wrist; awake; base; computerized; cost; density; design; healthy volunteer; improved; kinematics; motor learning; nervous system disorder; neural circuit; neuroimaging; non rapid eye movement; novel; pressure; programs; response; sequence learning; sleep regulation; social; synaptic depression; time use; visual motor

We spend a third of our life asleep, and even partial sleep deprivation has serious consequences on cognition, mood, and health, suggesting that sleep must serve some fundamental functions. Unfortunately, we lack a neurobiological understanding of what these functions might be. However, we know that sleep is tightly regulated as a function of prior wakefulness, suggesting that it may be needed to reverse some changes that take place when we are awake. We also know that the organ that has the greatest need for sleep is the brain, although we still do not know why. The overall goal of this project is to test a recent, comprehensive hypothesis about thefunction of non-rapid eyemovement sleep - the synaptic homeostasis hypothesis. According to the hypothesis, the brain needs to sleep because of the progressive strengthening of neural circuits that occurs during wakefulness and the associated energy and performance costs. We will test some key prediction of the hypothesis by using a novel method for performing high-density sleep electroencephalography (hd-EEG, 256 channels). We will take advantage of the well-known fact that sleep need is reflected by the amount of slow wave activity (SWA) in the sleep EEG. Specifically, we will test the prediction that procedures leading to local increases in synaptic strength, such as learning tasks involving particular brain regions, should lead to a local increase in sleep SWA. We will use both an implicit learning task (rotation adaptation) involving right parietal cortex, and an explicit learning task involving prefrontal cortex (motor sequence learning). We will then test the converse prediction that procedures leading to a local depression of synaptic circuits, such as arm immobilization, should lead to a local decrease in SWA during subsequent sleep. If these predictions are confirmed, they will provide strong evidence that sleep SWA is regulated at a local level, that its regulation is tied to plastic changes in cortical circuits, and that the level of local SWA has important consequences on performance after sleep. The results provided by this project will lend strong support to the synaptic homeostasis hypothesis and greatly advance our understanding of the functions of sleep at the fundamental level. There is overwhelming evidence that good, restorative sleep is exceedingly important to human health, that sleep deprivation and sleep restriction have enormous social costs, that sleep disorders are extremely common, and that they are frequently associated with psychiatric and neurological disorders. By tying brain plasticity to local sleep regulation, the results of these investigations will provide a novel, rational basis for designing therapeutic approaches aimed at enhancing the restorative value of sleep in health and disease. Thus, they are highly relevant to the mission of MINDS, NIMH, and NHLBI.

我们一生中三分之一的时间都在睡眠中度过，即使是部分睡眠不足也会对身体造成严重后果 认知、情绪和健康，表明睡眠必须发挥一些基本功能。很遗憾， 我们对这些功能缺乏神经生物学的理解。然而我们知道，睡眠是 作为先前觉醒的函数进行严格调节，这表明可能需要逆转一些 当我们清醒时发生的变化。我们还知道，最需要的器官 睡眠是大脑的一部分，虽然我们还不知道为什么。该项目的总体目标是测试最近的、 非快速动眼睡眠功能的综合假说——突触稳态 假设。根据假设，大脑需要睡眠是因为渐进强化 清醒期间发生的神经回路以及相关的能量和性能成本。我们将 通过使用一种执行高密度睡眠的新方法来测试该假设的一些关键预测 脑电图（HD-EEG，256 通道）。我们将利用众所周知的事实，即睡眠 睡眠脑电图中的慢波活动 (SWA) 量反映了需求。具体来说，我们将测试 预测导致局部突触强度增加的程序，例如涉及的学习任务 特定的大脑区域，应该会导致睡眠 SWA 的局部增加。我们将使用隐式学习 涉及右顶叶皮层的任务（旋转适应），以及涉及前额叶的显性学习任务 皮层（运动序列学习）。然后我们将测试相反的预测，即导致本地的程序 突触回路的抑制，例如手臂固定，应该会导致 SWA 的局部减少 随后的睡眠。如果这些预测得到证实，它们将提供强有力的证据证明睡眠 SWA 是 在地方一级进行监管，其监管与皮质回路的可塑性变化有关，并且 局部 SWA 对睡眠后的表现有重要影响。该项目提供的结果将 为突触稳态假说提供了强有力的支持，并极大地增进了我们对突触稳态的理解 睡眠的基本功能。 大量证据表明，良好的恢复性睡眠对人类健康极其重要， 睡眠剥夺和睡眠限制造成巨大的社会成本，睡眠障碍极其严重 常见，并且它们经常与精神和神经系统疾病相关。通过绑脑 局部睡眠调节的可塑性，这些研究的结果将为 设计旨在增强睡眠对健康和疾病的恢复价值的治疗方法。 因此，它们与 MINDS、NIMH 和 NHLBI 的使命高度相关。