NIH Director's Pioneer Award

我打算解决的问题是睡眠的功能，这是一个仍未解决的生物学难题。具体来说，我 打算测试一个关于睡眠用途的全面、新颖的假说，称为突触内稳态 假说(Tononi和Cirelli，Brain Res Bull 2003，睡眠医学修订版，2005)。这一假说解释了 许多关于睡眠及其调节的事实，从行为和系统发育证据到电生理和 分子观察，并对健康和疾病具有根本意义。这一假设很耐人寻味 与基础和临床神经科学相关的预测，我建议使用以下工具来测试这些预测 几种相辅相成的方法。如果这一假说通过了测试，我们可能第一次有了一个坚实的 科学地解释了为什么我们需要睡觉。 从科学的角度理解睡眠的功能显然是很重要的 人类健康。睡眠是一种普遍的、普遍的和基本的行为：它占据了我们生活的三分之一，而 在婴儿中的比例更高；它存在于所有研究过它的动物物种中，从果蝇到 人类；它受到严格的监管，这从长时间睡眠压力的不可抗拒的增加中可见一斑 失眠；甚至部分睡眠不足都会对认知、情绪和健康造成严重后果。 虽然所有现有的证据表明，睡眠是大脑的，是大脑的，对于大脑来说，睡眠的功能 尽管进行了数十年的密集研究，但睡眠状况仍不得而知。还没有这样全面的理论被提出来 这就是为什么突触动态平衡假说，如果得到证实，可能会构成一个亟需的 突破。 事实上，缺乏对我们为什么需要睡眠的理解不仅从科学的角度来看是有问题的， 但也是因为它对公共健康的巨大影响。数百万人抱怨睡眠问题，来自 失眠到白天过度困倦，从慢性疲劳到易怒与睡眠不满意有关。 睡眠问题是几种精神障碍的一个重要方面，特别是情绪障碍和焦虑 精神错乱。最后，睡眠不足有很高的社会成本，从驾驶和与工作有关的事故到长期的 表现不佳。因此，很大一部分人口经常接受旨在改善病情的药物治疗。 睡眠，或者在面对睡眠压力的情况下保持清醒。然而，这样的治疗受到我们的 对睡眠功能的无知。哪些睡眠障碍应该认真对待，因为它们 反映功能受损，如果有的话，不会严重干扰执行的功能 睡了吗？哪些睡眠异常可能会产生神经生物学后果，从而导致精神疾病 像抑郁症这样的疾病？最后，哪些方面的睡眠应该通过药物或药物来增强 行为疗法，我们应该考虑什么指标来确定它们的有效性？

The problem I intend to address is the function of sleep, a biological puzzle that is still unsolved. Specifically, I intend to test a comprehensive, novel hypothesis about what sleep is for, called the synaptic homeostasis hypothesis (Tononi and Cirelli, Brain Res Bull 2003, Sleep Medicine Rev., 2005). The hypothesis accounts for many facts about sleep and its regulation, from behavioral and phylogenetic evidence to electrophysiological and molecular observations, and has fundamental implications for health and disease. The hypothesis makes intriguing predictions that are relevant for both basic and clinical neuroscience, and I propose to test such predictions using several complementary approaches. If the hypothesis survives the tests, we may have for the first time a solid scientific explanation of why we need to sleep. Understanding the function of sleep is obviously important both scientifically and from the perspective of human health. Sleep is a pervasive, universal, and fundamental behavior: It occupies a third of our life, and an even larger proportion in infants; it is present in every animal species where it has been studied, from fruit flies to humans; it is tightly regulated, as indicated by the irresistible mounting of sleep pressure after prolonged wakefulness; and even partial deprivation of sleep has serious consequences on cognition, mood, and health. While all available evidence indicates that sleep is of the brain, by the brain, and for the brain, the function of sleep remains unknown despite decades of intensive research. No comprehensive theory had been advanced so far, which is why the synaptic homeostasis hypothesis, if corroborated, may constitute a much needed breakthrough. In fact, the lack of understanding of why we need to sleep is problematic not only from a scientific viewpoint, but also because of its vast implications for public health. Millions of people complain of sleep problems, from insomnia to excessive daytime sleepiness, from chronic fatigue to irritability associated with unsatisfactory sleep. Sleep problems are an important aspect of several psychiatric disorders, notably mood disorders and anxiety disorders. Finally, sleep deprivation has high social costs, from driving and work-related accidents to chronically poor performance. A large segment of the population is therefore treated routinely with drugs aimed at improving sleep, or at maintaining wakefulness in the face of sleep pressure. However, such treatments are hampered by our ignorance concerning the functions of sleep. Which sleep disturbances should be taken seriously because they reflect a functional impairment and which, if any, do not interfere significantly with the functions carried out by sleep? Which abnormalities of sleep are likely to have neurobiological consequences that can lead to psychiatric disorders such as depression? And finally, what aspect of sleep should be enhanced by pharmacological or behavioral treatments, and what indices should we consider to determine their effectiveness?