Local Sleep Regulation and Brain Plasticity

我们一生中有三分之一的时间都在睡觉，即使是部分睡眠不足也会造成严重的后果。 认知，情绪和健康，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，我们知道睡眠是 作为先前清醒的功能受到严格调节，这表明可能需要它来逆转一些 这些变化发生在我们清醒的时候。我们也知道最需要的器官 睡眠是大脑，虽然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， 关于非快速眼动睡眠功能的综合假说--突触稳态 假说.根据这一假说，大脑需要睡眠是因为进行性强化 以及相关的能量和性能成本。我们将 通过使用一种新的高密度睡眠方法来测试该假设的一些关键预测 脑电图（hd-EEG，256通道）。我们将利用众所周知的事实， 睡眠EEG中的慢波活动（SWA）的量反映了需求。具体来说，我们将测试 预测导致突触强度局部增加的程序，例如涉及 特别是大脑区域，应该会导致睡眠SWA的局部增加。我们将使用内隐学习和 任务（旋转适应）涉及右顶叶皮层，和一个明确的学习任务，涉及前额叶 运动序列学习（Motor Sequence Learning）然后，我们将测试匡威的预测，程序导致一个本地 突触回路的抑制，如手臂固定，应导致SWA的局部减少， 随后的睡眠。如果这些预测得到证实，他们将提供强有力的证据，睡眠SWA是 在局部水平上进行调节，其调节与皮质回路的可塑性变化有关， 局部SWA对睡眠后的表现有重要影响。该项目提供的结果将 为突触内稳态假说提供了有力的支持，并大大推进了我们对突触内稳态的理解。 睡眠的基本功能。 有压倒性的证据表明，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具有巨大社会成本， 常见的，他们经常与精神和神经系统疾病。通过将大脑 可塑性局部睡眠调节，这些调查的结果将提供一个新的，合理的基础， 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MINDS、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.