Local Sleep Regulation and Brain Plasticity

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。不幸的是，我们缺乏对这些功能的神经生物学理解。然而，我们知道睡眠受到严格的调节，作为清醒前的功能，这表明可能需要逆转我们醒着时发生的一些变化。我们也知道最需要睡眠的器官是大脑，尽管我们仍然不知道为什么。这个项目的总体目标是测试一个最近的，关于非快速眼动睡眠功能的综合假设-突触稳态假设。根据这一假说，大脑需要睡眠，因为在清醒时神经回路会逐渐加强，并且会消耗相应的能量和性能。我们将通过使用一种新的方法进行高密度睡眠脑电图（hd-EEG， 256通道）来测试该假设的一些关键预测。我们将利用众所周知的事实，即睡眠需求是由睡眠脑电图中的慢波活动（SWA）的数量反映出来的。具体来说，我们将测试导致局部突触强度增加的过程的预测，例如涉及特定大脑区域的学习任务，应该导致局部睡眠SWA增加。我们将使用涉及右顶叶皮层的内隐学习任务（旋转适应）和涉及前额叶皮层的外显学习任务（运动序列学习）。然后，我们将测试相反的预测，即导致局部突触回路抑制的过程，如手臂固定，应该导致随后睡眠中的局部SWA减少。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在局部水平受到调节，其调节与皮质回路的可塑性变化有关，局部SWA水平对睡眠后的表现有重要影响。本项目提供的结果将有力地支持突触内稳态假说，并极大地促进我们在基础水平上对睡眠功能的理解。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会带来巨大的社会成本，睡眠障碍极其普遍，而且往往与精神和神经系统疾病有关。通过将大脑可塑性与局部睡眠调节联系起来，这些研究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提供新颖、合理的基础。因此，它们与NINDS、NIMH和NHLBI的使命高度相关。

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. 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 the function of non-rapid eye movement 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 NINDS, NIMH, and NHLBI.