Brain Plasticity and Local Sleep Homeostasis: An Electrophysiological Perspective

大脑可塑性和局部睡眠稳态：电生理学视角

• 批准号: 7991360
• 负责人: Eric C Landsness
• 金额: $ 4.6万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7991360
• 关键词: Acoustic Stimulation; Acoustics; Area; Biological Process; Brain; Cerebral cortex; Cognition; Computers; Consumption; Disease; Electroencephalography; Event; Goals; Health; Homeostasis; Human; Investigation; Lead; Learning; Life; Link; Location; Magnetic Resonance Imaging; Memory; Mental disorders; Mentors; Metabolic; Middle Insomnia; Moods; Neurobiology; Neurons; Noise; Parietal Lobe; Performance; Plastics; Play; Process; Regulation; Role; Rotation; Signal Transduction; Sleep; Sleep Deprivation; Sleep Disorders; Slow-Wave Sleep; Stage II Sleep; Stimulus; Synapses; Synaptic plasticity; Testing; Therapeutic; Time; Wakefulness; Weight; awake; base; computerized; cost; density; deprivation; design; human subject; kinematics; motor control; nervous system disorder; neural circuit; non rapid eye movement; pressure; prevent; research study; sleep regulation; social; visual motor

DESCRIPTION (provided by applicant): 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. Presently, we lack a neurobiological understanding of what these functions might be. We know that sleep is tightly regulated as a function of prior wakefulness and sleep pressure is reflected by the amount of slow wave activity (SWA) in the EEG of non-rapid eye movement (NREM) sleep. SWA (the EEG power density between 0.5 and 4.5 Hz) increases in proportion to the time spent awake and decreases during sleep, but why this is the case remains unclear. The overall goal of this proposal is to test a recent hypothesis concerning the function of NREM sleep - the synaptic homeostasis hypothesis (SHY). The hypothesis states that plastic processes during wakefulness result in a net increase in synaptic strength in many brain circuits; such increased synaptic weight comes at the expense of increased metabolic consumption. Strengthened brain circuits lead to larger SWA during subsequent sleep. In turn, sleep SWA renormalizes synaptic strength to a baseline level that is energetically sustainable and beneficial for memory and performance. This proposal will test two predictions of SHY: sleep slow waves are necessary for the renormalization of cortical circuits after learning (Aim 1); and sleep slow waves are necessary for the enhancement of performance after sleep (Aim 2). To do so, I will use high density EEG recordings in humans while performing a visuomotor learning task (rotation learning) that involves right parietal cortex and during post learning sleep. Sleep slow waves will be suppressed using mild acoustic stimuli that do not fragment sleep. Control experiments will apply the same number of stimuli during stage 2 sleep. The specific aims are designed to evaluate if, as predicted by SHY, learning leaves a local trace in the waking EEG that is renormalized after sleep, and if the selective deprivation of sleep slow waves leads to a persistence of such EEG traces and to a suppression of post-sleep performance enhancement. PUBLIC HEALTH RELEVANCE: There is overwhelming evidence that restorative sleep is necessary to human health, that sleep deprivation and restriction have enormous social costs, and that sleep disorders are extremely common and are frequently associated with psychiatric and neurological disorders. By tying brain plasticity and performance to SWA, the results of this investigation will advance our understanding of the function of sleep at a fundamental level, lend support to SHY, and provide a rational basis for designing therapeutic approaches that focus on the quality of SWA and enhance the restorative effects of sleep in health and disease.

我们一生中有三分之一的时间是在睡眠中度过的，即使是部分睡眠不足也会对认知、情绪和健康产生严重后果，这表明睡眠必须具有一些基本功能。目前，我们缺乏对这些功能的神经生物学理解。我们知道，睡眠是作为先前觉醒的函数而被严格调节的，并且睡眠压力由非快速眼动（NREM）睡眠的EEG中的慢波活动（SWA）的量来反映。SWA（0.5至4.5 Hz之间的EEG功率密度）与清醒时间成比例增加，并在睡眠期间减少，但为什么会出现这种情况仍不清楚。这项提议的总体目标是测试最近关于NREM睡眠功能的假说-突触稳态假说（SHY）。该假说指出，清醒时的可塑性过程导致许多脑回路中突触强度的净增加;这种突触重量的增加是以代谢消耗增加为代价的。强化的大脑回路在随后的睡眠中导致更大的SWA。反过来，睡眠SWA将突触强度重新正常化到能量可持续且有益于记忆和表现的基线水平。该提案将测试SHY的两个预测：睡眠慢波是学习后皮质回路重新正常化所必需的（目标1）;睡眠慢波是睡眠后性能增强所必需的（目标2）。为此，我将使用高密度脑电图记录在人类，同时执行视觉学习任务（旋转学习），涉及右顶叶皮层和学习后睡眠。睡眠慢波将被抑制使用温和的声音刺激，不碎片睡眠。控制实验将在第二阶段睡眠期间施加相同数量的刺激。具体的目的是评估，如果如预测的SHY，学习离开一个本地的痕迹在清醒的脑电图，是重新规范后的睡眠，如果睡眠慢波的选择性剥夺导致持久性这样的脑电图痕迹和抑制后睡眠性能增强。公共卫生关系：有大量证据表明，恢复性睡眠对人类健康是必要的，睡眠剥夺和限制有巨大的社会成本，睡眠障碍非常常见，经常与精神和神经系统疾病有关。通过将大脑可塑性和表现与SWA联系起来，这项调查的结果将促进我们对睡眠功能的基本理解，为SHY提供支持，并为设计专注于SWA质量的治疗方法提供合理的基础，并增强睡眠在健康和疾病中的恢复作用。