Brain Plasticity and Local Sleep Homeostasis: An Electrophysiological Perspective

描述（由申请人提供）：我们一生中三分之一的时间都在睡眠中度过，即使部分睡眠不足也会对认知、情绪和健康产生严重影响，这表明睡眠必须发挥一些基本功能。目前，我们对这些功能缺乏神经生物学的理解。我们知道，睡眠受到先前清醒状态的严格调节，睡眠压力由非快速眼动 (NREM) 睡眠脑电图中的慢波活动 (SWA) 量反映出来。 SWA（0.5 至 4.5 Hz 之间的脑电图功率密度）随着清醒时间的增加而增加，在睡眠期间减少，但为什么会出现这种情况仍不清楚。该提案的总体目标是检验最近关于 NREM 睡眠功能的假设 - 突触稳态假说 (SHY)。该假说指出，清醒期间的可塑过程会导致许多大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。强化的大脑回路会导致随后睡眠期间的 SWA 更大。反过来，睡眠 SWA 将突触强度重新正常化至基线水平，该水平在能量上可持续且有益于记忆和表现。该提案将测试 SHY 的两个预测：睡眠慢波对于学习后皮质回路的重新正常化是必要的（目标 1）；睡眠慢波对于睡眠后表现的增强是必要的（目标2）。为此，我将在人类执行涉及右顶叶皮层的视觉运动学习任务（旋转学习）时以及学习后睡眠期间使用高密度脑电图记录。使用不会破坏睡眠的温和声刺激可以抑制睡眠慢波。对照实验将在第二阶段睡眠期间施加相同数量的刺激。具体目标旨在评估学习是否如 SHY 所预测的那样，在睡眠后重新正常化的清醒脑电图中留下局部痕迹，以及选择性剥夺睡眠慢波是否会导致此类脑电图痕迹持续存在并抑制睡眠后表现的增强。公共卫生相关性：大量证据表明，恢复性睡眠对人类健康至关重要，睡眠剥夺和限制会造成巨大的社会成本，睡眠障碍极为常见，并且经常与精神和神经系统疾病相关。通过将大脑可塑性和表现与 SWA 联系起来，这项研究的结果将从根本上增进我们对睡眠功能的理解，为 SHY 提供支持，并为设计关注 SWA 质量和增强睡眠对健康和疾病的恢复作用的治疗方法提供合理的基础。

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.