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

描述（由申请人提供）：关于睡眠的功能尚无共识。这是睡眠临床和基础科学研究的核心问题。近年来，一种越来越流行的假设是，所有动物睡觉都是出于同样的原因，尽管其中的原因尚未被发现。由此可以得出一个合理的结论：对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数据库中搜索单词“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支持的关于哺乳动物睡眠的工作，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。在哺乳动物和无脊椎动物中，类似的遗传机制无疑是控制类睡眠状态的某些方面的基础，对果蝇、斑马鱼和秀丽隐杆线虫的研究也揭示了这一点。然而，我们最近的工作和对文献的分析为睡眠行为、生理和神经化学的巨大多样性提供了证据。在快速眼动和非快速眼动睡眠、睡眠反弹和睡眠脑电图的存在和调节方面，哺乳动物之间也存在重大差异。在比较海洋和陆地哺乳动物时，这种多样性尤为明显。特别有趣的是海狗和其他耳类动物的睡眠。当它们在陆地上时，这些动物有双侧睡眠，与狗和其他被研究的哺乳动物的睡眠没有什么区别，但当它们在水中时，它们有半脑非快速眼动睡眠，在很长一段时间内很少或没有快速眼动睡眠。这种与正常哺乳动物睡眠模式的惊人偏离，在海狗返回陆地时不会产生任何不良影响，也不会出现任何睡眠反弹。对这些哺乳动物的单半球睡眠的研究将使我们第一次能够清楚地区分与睡眠状态相关的神经元机制与与行为静止相关的神经元机制，这些行为静止与心率、肌肉张力、呼吸和体温降低有关。它们将使我们能够识别猫、老鼠、人类和海狗共有的睡眠的核心解剖学、神经化学和神经生理学因素，以及海狗特有的任何神经控制机制。为了实现这些目标，我们将使用双侧体内微透析来监测这些状态下关键神经递质的释放，Fos免疫组织化学来鉴定在单半球睡眠、双半球睡眠和清醒期间活跃的细胞群，以及脑干和前脑温度测量来确定与这些状态相关的温度调节变化。只有了解哺乳动物睡眠的多样性和共性，才能全面了解人类睡眠的进化、调节和功能。

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.