Harvard Center on Sleep Neurobiology and Sleep Apnea (S*

描述（由申请人提供）： 人们普遍认为，阻塞性睡眠呼吸暂停发展的关键事件是从清醒到睡眠过渡期间上气道扩张肌活动的丧失。这导致咽部气道关闭，导致缺氧、高碳酸血症和呼吸努力增加。这些后果触发了一系列保护性脑干反应，包括心血管反射和行为觉醒，导致咽扩张肌活动恢复，气道通畅恢复和通气恢复。如果在夜间重复多次，这一过程会导致睡眠碎片化和潜在的不良心血管事件。 我们的提案包括六个项目和四个核心，都涉及睡眠、睡眠呼吸暂停或其后果的各个方面。项目。1解决了睡眠呼吸暂停的病理生理学检查上呼吸道肌肉控制和肺容量的变化发生在人类睡眠。项目2将评估大鼠间歇性缺氧和睡眠中断对行为、生理、细胞外腺苷和神经功能的影响。项目3提出了控制细胞外腺苷的机制，主要集中在一氧化氮在这一过程中的作用。项目4利用啮齿动物睡眠片段的稳定模型检查行为、学习、生理和神经化学。项目。5将使用新的分子技术评估食欲素调节小鼠睡眠/觉醒的机制。项目。6阐述了大鼠上呼吸道反射的解剖学和神经调节，再次阐述了睡眠呼吸暂停的病理生理学。核心A是行政核心，负责监督财政、统计和科学领域。核心B将处理项目2、3、5和6的所有神经解剖学研究。核心C，我们的行为核心，将为项目2，4和5提供啮齿动物行为评估。最后，核心D是一个切片电生理核心，将为项目2、3、4和5提供此类测试。从核心中可以明显看出，该SCOR有一套高度集成的项目，这些项目应能在临床和基础科学水平上大大提高我们对睡眠呼吸暂停及其后果的理解。

DESCRIPTION (provided by applicant): It is widely agreed that the key event in the development of obstructive sleep apnea is a loss of upper airway dilator muscle activity in the transition from wakefulness to sleep. This produces pharyngeal airway closure resulting in hypoxia, hypercapnia and increasing respiratory effort. These consequences trigger a set of protective brainstem responses including cardiovascular reflexes and behavioral arousal resulting in restitution of pharyngeal dilator muscle activity, a return of airway patency, and a resumption of ventilation. When repeated many times over the course of the night this process leads to fragmented sleep and potentially adverse cardiovascular events. Our proposal consists of six Projects and four Cores all addressing various aspects of sleep, sleep apnea, or its consequences. Proj. 1 addresses the pathophysiology of sleep apnea examining upper airway muscle control and lung volume changes occurring during sleep in humans. Proj. 2 will assess the impact of both intermittent hypoxia and sleep interruption in rats on behavior, physiology, extracellular adenosine, and neural function. Proj. 3 addresses the mechanisms controlling extmcellular adenosine, focussing primarily on the role of nitric oxide in this process. Proj. 4 utilizes a stable model of rodent sleep fragmentation examining behavior, learning, physiology, and neurochemistry. Proj. 5 will assess the mechanisms by which orexin regulates sleep/wake in the mouse using novel molecular techniques. Proj. 6 addresses the anatomy and neuromodulation of upper airway reflexes in the rat again addressing the pathophysiology of sleep apnea. Core A, the Administrative Core, oversees the financial, statistical and scientific areas. Core B will handle all neuroanatomic studies for Projects 2, 3, 5, and 6. Core C, our Behavioral Core, will provide rodent behavioral assessment for Projects 2, 4, and 5. Finally, Core D is a slice Electrophysiology Core and will provide such testing to Projects 2, 3, 4, and 5. As should be evident from the Cores, this SCOR has a high integrated set of Projects that should substantially improve our understanding of sleep apnea and its consequences at a clinical and basic science level.