Unihemispheric sleep: implications for mechanisms of sleep control and function i

描述（由申请人提供）：关于睡眠的功能没有共识。这是睡眠的临床和基础科学研究的核心问题。近年来，一种假设越来越流行，即所有动物的睡眠原因都是一样的，尽管这个原因还没有被发现。这导致了合理的结论，即睡眠和睡眠功能的研究应该集中在最简单的动物身上。在CRISP数据库中搜索“果蝇”和“睡眠”，列出了38个NIH项目。然而，我不知道目前有任何NIH支持的哺乳动物睡眠研究工作，除了已经很好理解的“标准实验室哺乳动物”，主要是啮齿动物，猫和灵长类动物。类似的遗传机制无疑是哺乳动物和无脊椎动物控制类睡眠状态的某些方面的基础，对果蝇、斑马鱼和C。优雅然而，我们最近的工作和对文献的分析为睡眠行为、生理学和神经化学的巨大多样性提供了证据。即使在哺乳动物物种之间，在REM和非REM睡眠、睡眠反弹和睡眠EEG的存在和调节方面也存在重大差异。这种多样性在比较海洋和陆地哺乳动物时尤为明显。特别令人感兴趣的是睡在海狗和其他otariids。这些动物在陆地上时的双侧睡眠与狗和其他被研究的哺乳动物没有区别，但当它们在水中时，它们有很长一段时间的单侧非REM睡眠和很少或没有REM睡眠。这种与哺乳动物正常睡眠模式的惊人偏离并没有产生任何不良影响，也没有在海狗回到陆地后出现任何睡眠反弹。对这些哺乳动物的单侧半球睡眠的研究将使我们首次能够清楚地区分与睡眠状态相关的神经机制和与行为静止相关的神经机制，以及与之相关的心率、肌张力、呼吸和体温降低。它们将使我们能够识别猫、大鼠、人类和海狗共同的睡眠的核心解剖学、神经化学和神经生理学元素，以及海狗特有的任何神经控制机制。在追求这些目标，我们将使用双边在体内微透析，以监测在这些国家的关键神经递质的释放，Fos免疫组化，以确定活跃在单半球睡眠，双半球睡眠和清醒的细胞群，脑干和前脑温度测量，以确定与这些国家相关的体温调节变化。只有了解哺乳动物睡眠的多样性和共同性，才能全面了解人类睡眠的进化、调节和功能。 公共卫生相关性：当海狗在水中时，它们一年中有6个月的家，它们一次只在大脑和身体的一半睡觉，大大减少或消除REM睡眠，并经常在几天内完全放弃睡眠，这种睡眠模式类似于鲸鱼和海豚。了解这种非常不寻常的睡眠模式是如何以及为什么会发生的，将为快速眼动睡眠和非快速眼动睡眠的功能提供基本的见解，这是睡眠研究中的关键谜团。它还将使我们能够确定在睡眠期间活跃的每个神经元组的位置和特定角色。这将对理解以人类REM睡眠异常为特征的疾病，包括嗜睡症，抑郁症和REM睡眠行为障碍产生影响。它还将提供对失眠原因的深入了解。

DESCRIPTION (provided by applicant): There is no consensus as to the function(s) of sleep. This is the central issue underlying both clinical and basic science investigations of sleep. One assumption that has become ascendant in recent years is that all animals sleep for the same reason, albeit a reason that has not yet been discovered. This leads to the reasonable conclusion that investigations of sleep and sleep function should be focused on the simplest animals. A search of the CRISP database for the words "Drosophila" and "sleep" lists 38 NIH programs. However, I am not aware of any current NIH supported work on sleep in mammals other than the already well understood "standard lab mammals," mostly rodents, cats and primates. Similar genetic mechanisms undoubtedly underlie some aspects of the control of sleep- like states in mammals and invertebrates and are being revealed by studies of Drosophila, zebrafish and C. elegans. However, our recent work and analysis of the literature presents evidence for a great diversity of sleep behavior, physiology and neurochemistry. Major differences exist even between mammalian species in terms of the presence and regulation of REM and nonREM sleep, sleep rebound and sleep EEG. This diversity is particularly obvious when comparing marine and land mammals. Of particular interest is sleep in the fur seal and other otariids. These animals have bilateral sleep that is indistinguishable from that seen in the dog and other studied mammals when they are on land, but when the are in water they have unihemispheric nonREM sleep and little or no REM sleep for very long periods of time. This startling deviation from the normal mammalian sleep pattern does not produce any ill effects or any sleep rebound when the fur seal returns to land. Investigation of unihemispheric sleep in these mammals will allow us to, for the first time, clearly distinguish neuronal mechanisms linked to the sleep state from those linked to behavioral quiescence with its associated heart rate, muscle tone, respiration and body temperature reductions. They will allow us to identify core anatomical, neurochemical and neurophysiological elements of sleep common to the cat, rat, human and fur seal, and any neurological control mechanisms unique to the fur seal. In pursuance of these objectives, we will use bilateral in vivo microdialysis to monitor the release of key neurotransmitters during these states, Fos immunohistochemistry to identify cell groups active during unihemispheric sleep, bihemispheric sleep and waking, and brainstem and forebrain temperature measurement to identify thermoregulatory changes correlated with these states. A full understanding of the evolution, regulation and function of sleep in humans can only be achieved by understanding the diversity and commonalities of mammalian sleep. PUBLIC HEALTH RELEVANCE: When fur seals are in water, their home for 6 months of the year, they have sleep in only one half of the brain and body at a time, greatly reduce or eliminate REM sleep and frequently forgo sleep entirely for periods of several days, a sleep pattern that resembles that of whales and dolphins. Understanding how and why this very unusual sleep pattern occurs will provide fundamental insights into the functions of REM and nonREM sleep, the key mysteries in sleep research. It will also allow us to determine the location and specific roles of each of the neuronal groups active during sleep. This would have implications for the understanding of diseases characterized by REM sleep abnormalities in humans, including narcolepsy, depression and REM sleep behavior disorder. It would also provide an insight into the causes of insomnia.