Brain Plasticity and Local Sleep Homeostasis: An Electrophysiological Perspective

描述(申请人提供)：我们一生中有三分之一的时间在睡觉，即使是部分睡眠不足也会对认知、情绪和健康造成严重后果，这表明睡眠必须发挥一些基本功能。目前，我们对这些功能可能是什么缺乏神经生物学上的了解。我们知道，睡眠受到事先清醒状态的严格控制，睡眠压力反映在非快速眼动(NREM)睡眠的脑电中的慢波活动量(SWA)。SWA(0.5至4.5赫兹之间的脑电功率密度)与醒着的时间成比例增加，而在睡眠中减少，但原因尚不清楚。这项提议的总体目标是测试最近关于NREM睡眠功能的一个假说--突触内稳态假说(SHY)。该假说指出，清醒时的可塑性过程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增加新陈代谢消耗为代价的。在随后的睡眠中，大脑回路的加强会导致更大的SWA。反过来，睡眠SWA将突触强度重新正常化到基线水平，这在能量上是可持续的，对记忆和表现有利。这一建议将检验害羞的两个预测：睡眠慢波是学习后皮层回路重整化所必需的(目标1)；睡眠慢波是提高睡眠后表现所必需的(目标2)。为此，我将使用人类的高密度脑电记录，同时执行涉及右顶叶皮质的视觉运动学习任务(旋转学习)，并在学习后睡眠期间。睡眠慢波将被抑制，使用温和的声音刺激，不会破坏睡眠。对照实验将在第二阶段睡眠中施加相同数量的刺激。这些特定的目标旨在评估是否如Shy预测的那样，学习在清醒的脑电中留下局部痕迹，并在睡眠后重新正规化，以及选择性地剥夺睡眠慢波是否导致这种脑电痕迹的持续和对睡眠后表现增强的抑制。公共卫生相关性：有压倒性的证据表明，恢复性睡眠对人类健康是必要的，剥夺和限制睡眠会带来巨大的社会成本，睡眠障碍非常常见，经常与精神和神经障碍有关。通过将大脑的可塑性和表现与SWA联系起来，本研究的结果将从根本上促进我们对睡眠功能的理解，支持Shy，并为设计专注于SWA质量的治疗方法提供合理的依据，并增强睡眠对健康和疾病的恢复效果。

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.