Local Sleep Regulation and Brain Plasticity

我们一生中三分之一的时间都在睡觉，即使是部分睡眠不足也会对健康造成严重影响 认知、情绪和健康，这表明睡眠必须发挥一些基本功能。不幸的是， 我们对这些功能可能是什么缺乏神经生物学上的理解。然而，我们知道睡眠是 作为先前觉醒的函数受到严格监管，这表明可能需要扭转一些 当我们醒着的时候发生的变化。我们还知道，最需要的器官 睡眠是大脑，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， 非快速眼动睡眠功能的综合假说--突触内稳态 假设。根据该假说，大脑需要睡眠，因为渐进性增强 清醒时出现的神经回路以及相关的能量和性能成本。我们会 使用一种执行高密度睡眠的新方法来测试该假设的一些关键预测 脑电(HD-EEG，256个导联)。我们将利用睡眠这一众所周知的事实 睡眠脑电中慢波活动(SWA)的数量反映了需求。具体地说，我们将测试 预测导致局部突触强度增加的程序，如涉及到的学习任务 特定的大脑区域，应该会导致局部睡眠SWA的增加。我们将使用两种内隐学习 涉及右侧顶叶皮质的旋转适应任务和涉及前额叶的外显学习任务 皮质(运动序列学习)。然后我们将测试反向预测，即程序导致局部 突触回路的抑制，如手臂的固定，应该会导致SWA在 随后的睡眠。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是 在地方层面上受到监管，其监管与大脑皮层回路的可塑性变化有关，而且 局部SWA对睡眠后的表现有重要影响。该项目提供的结果将 有力地支持了突触动态平衡假说，并极大地促进了我们对 睡眠在基本层面上的功能。 有压倒性的证据表明，良好的恢复睡眠对人类健康极其重要， 睡眠剥夺和睡眠限制有巨大的社会代价，睡眠障碍是极其严重的 常见，而且常常与精神和神经障碍有关。通过捆绑大脑 对局部睡眠调节的可塑性，这些研究结果将为临床提供新的、合理的依据 设计治疗方法，旨在提高睡眠对健康和疾病的恢复价值。 因此，它们与思维、NIMH和NHLBI的使命高度相关。

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 thefunction of non-rapid eyemovement 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 MINDS, NIMH, and NHLBI.