Brain Plasticity and Local Sleep Homeostasis: An Electrophysiological Perspective

描述（由申请人提供）：我们一生中有三分之一的时间是在睡眠中度过的，即使是部分睡眠剥夺也会对认知、情绪和健康产生严重影响，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可能是什么的神经生物学理解。我们知道睡眠受到严格的调节，作为先前清醒的功能，睡眠压力通过非快速眼动（NREM）睡眠时脑电图中的慢波活动（SWA）的数量反映出来。SWA（脑电图功率密度在0.5和4.5赫兹之间）随着清醒时间的增加而增加，而在睡眠期间减少，但为什么会出现这种情况尚不清楚。本研究的总体目标是验证最近关于非快速眼动睡眠功能的假说——突触稳态假说（SHY）。该假说认为，在清醒状态下的可塑性过程导致许多脑回路中突触强度的净增加；突触重量的增加是以增加代谢消耗为代价的。在随后的睡眠中，强化的大脑回路会导致更大的SWA。反过来，睡眠SWA将突触强度重新规范化到一个能量可持续和有利于记忆和表现的基线水平。这一提议将测试两个关于害羞的预测：睡眠慢波对于学习后皮层回路的重整是必要的（目的1）；睡眠慢波是增强睡眠后表现所必需的（目的2）。为了做到这一点，我将在人类执行视觉运动学习任务（旋转学习）时使用高密度脑电图记录，该任务涉及右顶叶皮层和学习后睡眠。使用不破坏睡眠的温和声刺激可以抑制睡眠慢波。控制实验将在第二阶段睡眠中施加相同数量的刺激。具体目的是评估是否如SHY所预测的那样，学习在清醒的脑电图中留下局部痕迹，并在睡眠后重新规范化，以及选择性剥夺睡眠慢波是否会导致这种脑电图痕迹的持续存在，并抑制睡眠后的表现增强。公共卫生相关性：大量证据表明，恢复性睡眠对人类健康是必要的，睡眠剥夺和睡眠限制会带来巨大的社会成本，睡眠障碍极为常见，往往与精神和神经疾病有关。通过将大脑的可塑性和表现与SWA联系起来，本研究的结果将在基础层面上推进我们对睡眠功能的理解，为SHY提供支持，并为设计专注于SWA质量的治疗方法和增强睡眠对健康和疾病的恢复作用提供合理的基础。

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.