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生的关键事件是从清醒到睡眠的转变过程中上呼吸道扩张肌活动的丧失。这会导致咽部呼吸道关闭，导致缺氧、高碳酸血症和增加呼吸努力。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唤醒，导致咽部扩张器肌肉活动的恢复，呼吸道通畅的恢复，以及呼吸的恢复。如果在夜间重复多次，这一过程会导致睡眠支离破碎，并可能导致不良的心血管事件。 我们的提案包括六个项目和四个核心，所有这些都涉及睡眠、睡眠呼吸暂停或其后果的各个方面。项目。1阐述睡眠呼吸暂停的病理生理学，检查人类睡眠期间发生的上呼吸道肌肉控制和肺容量变化。项目。2将评估间歇性低氧和睡眠中断对大鼠行为、生理、细胞外腺苷和神经功能的影响。项目。3阐述了控制胞外腺苷的机制，主要集中在一氧化氮在这一过程中的作用。项目。4利用一种稳定的啮齿动物睡眠碎片模型来检测行为、学习、生理和神经化学。项目。5将使用新的分子技术评估增食欲素调节小鼠睡眠/觉醒的机制。项目。6讨论了大鼠上呼吸道反射的解剖学和神经调节，再次讨论了睡眠呼吸暂停的病理生理学。核心A是行政核心，负责监督财务、统计和科学领域。核心B将负责项目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是一个切片电生理学核心，将为项目2、3、4和5提供此类测试。从核心应该可以看出，SCOR有一套高度集成的项目，应该在临床和基础科学水平上大幅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.