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

单半球睡眠：对睡眠控制和功能机制的影响

• 批准号: 8077971
• 负责人: JEROME M SIEGEL
• 金额: $ 43.92万
• 依托单位: SEPULVEDA RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8077971
• 关键词: Abbreviations; Acetylcholine; Amygdaloid structure; Animals; Basic Science; Behavior; Behavioral; Bilateral; Body Temperature; Brain; Brain Stem; Caenorhabditis elegans; Canis familiaris; Cells; Clinical Sciences; Computer Retrieval of Information on Scientific Projects Database; Consensus; Contralateral; Databases; Disease; Dolphins; Dopamine; Drosophila genus; Electroencephalography; Elements; Evolution; Felis catus; Fur Seals; Genetic; Glutamates; Heart Rate; Histamine; Home environment; Human; Hypothalamic structure; Immunohistochemistry; Invertebrates; Investigation; Ipsilateral; Label; Left; Link; Literature; Location; Mammals; Marines; Measurement; Measures; Medial; Mental Depression; Metabolism; Microdialysis; Monitor; Muscle Tonus; Narcolepsy; Neurologic; Neurons; Neurotransmitters; Norepinephrine; Pattern; Physiology; Pontine structure; Population; Primates; Procedures; Prosencephalon; REM Sleep; REM Sleep Behavior Disorder; Rattus; Regulation; Research; Respiration; Rodent; Role; Serotonin; Side; Sleep; Sleeplessness; Slow-Wave Sleep; Temperature; Time; United States National Institutes of Health; Water; Whales; Work; Zebrafish; basal forebrain; cholinergic; hypocretin; in vivo; insight; interest; locus ceruleus structure; melanin-concentrating hormone; neurochemistry; neurophysiology; neurotransmitter release; noradrenergic; prevent; programs; public health relevance; sleep abnormalities; sleep regulation; voltage

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.

描述（由申请人提供）：关于睡眠功能尚无共识。这是临床和基础科学睡眠研究的基础问题。近年来已经成为上升的一个假设是，所有动物的睡眠都是出于相同的原因，尽管这是尚未发现的原因。这得出了一个合理的结论，即睡眠和睡眠功能的研究应集中在最简单的动物上。搜索Crisp数据库中的“果蝇”和“睡眠”列出了38个NIH程序。但是，除了已经了解到的“标准实验室哺乳动物”（主要是啮齿动物，猫和灵长类动物）以外，我不知道当前的NIH是否支持哺乳动物的睡眠工作。毫无疑问，类似的遗传机制是控制睡眠状态和无脊椎动物中的状态的某些方面的基础，并且正在果蝇，斑马鱼和秀丽隐杆线虫的研究揭示。但是，我们最近对文献的工作和分析为睡眠行为，生理和神经化学的多样性提供了证据。在REM和非REM睡眠，睡眠反弹和睡眠脑电图的存在和调节方面，哺乳动物物种之间的主要差异也存在。在比较海洋和陆地哺乳动物时，这种多样性尤其明显。特别感兴趣的是在海豹和其他耳齿中睡觉。这些动物的双侧睡眠与狗和其他研究的哺乳动物在陆地上时所见，但是当它们在水中时，它们的无限性非REM睡眠，很少或根本没有REM睡觉。与正常哺乳动物的睡眠方式相对于正常的哺乳动物睡眠模式，当皮草封印返回陆地时，不会产生任何不良影响或任何睡眠反弹。对这些哺乳动物中无际睡眠的研究将使我们首次清楚地区分与睡眠状态相关的神经元机制，即与行为静止的那些与其相关的心率，肌肉张力，呼吸和体温降低相关的神经元机制。它们将使我们能够识别猫，大鼠，人类和皮草密封的共同的睡眠的核心解剖学，神经化学和神经生理元素，以及毛密封特有的任何神经系统控制机制。为了实现这些目标，我们将使用双边体内微透析来监测这些州期间关键神经递质的释放，FOS免疫组织化学在不相互症状的睡眠期间识别活跃的细胞组，双性恋睡眠，双性恋睡眠和醒来，醒来，脑干和脑干和脑干和前体测量，以确定这些状态与这些状态更改为众所周知的热量相关。只有通过了解哺乳动物睡眠的多样性和共同点，才能完全了解人类睡眠的演变，调节和功能。 公共卫生相关性：当皮草海豹在水中，一年中的6个月内，他们一次只有一半的大脑和身体睡眠，大大减少或消除了REM睡眠，并且经常完全放弃几天的时间，这种睡眠模式类似于鲸鱼和海豚的睡眠方式。了解这种非常不寻常的睡眠模式的方式以及为什么会为REM和非REM睡眠功能（睡眠研究的关键奥秘）提供基本见解。它还将使我们能够确定睡眠期间每个神经元组的位置和特定作用。这将对理解人类的REM睡眠异常（包括发肠炎，抑郁症和REM睡眠行为障碍）的理解具有影响。这也将提供对失眠原因的见解。