Plasticity in the central neural control of the upper airway

阻塞性睡眠呼吸暂停（OSA）是一种常见的疾病，影响儿童和成人。其主要表现是患者在睡眠期间无法保持气道开放，导致睡眠丧失和碎片化，警觉性受损，动脉高血压和代谢紊乱。阻塞性睡眠呼吸暂停的状态依赖性指出了睡眠-觉醒状态控制和呼吸控制之间相互作用的核心作用。阻塞性睡眠呼吸暂停患者睡眠不足，上呼吸道肌肉活动适应性增加。尽管后一种适应有助于他们在清醒时保持正常呼吸，但睡眠的增加会通过增加与睡眠相关的上呼吸道阻塞的频率和严重程度来加剧OSA状况，这些现象已经被广泛描述和讨论，但人类研究的能力有限，无法阐明潜在的细胞，神经化学和分子机制。计划中的研究的目标是使用啮齿动物模型揭示负责改变上呼吸道控制的中枢神经机制。这些研究将结合联合收割机对长期使用仪器的大鼠睡眠-觉醒周期中上呼吸道肌肉活动的监测，以及对负责控制上呼吸道的大脑区域中基因和蛋白质表达的定量研究。为了模拟类似于OSA患者的条件，啮齿动物将受到操纵，如睡眠剥夺，暴露于交替的氧气水平和增加上气道肌肉负荷的手术干预。

Obstructive sleep apnea (OSA) is a common disorder that affects both children and adults. Its main manifestation is the patients’ inability to maintain the airway open during sleep leading to sleep loss and fragmentation, impaired alertness, arterial hypertension and metabolic disorders. The state-dependence of OSA points to a central role of the interaction between control of sleep-wake states and control of breathing. OSA patients are sleep-deprived and develop an adaptive increase in the activity of their upper airway muscles. Whereas the latter adaptation helps them maintain normal breathing during wakefulness, the increased drive for sleep exacerbates OSA conditions by increasing frequency and severity of sleep-related upper airway obstructions.These phenomena have been extensively described and discussed, but studies in humans are limited in their ability to elucidate the underlying cellular, neurochemical and molecular mechanisms. The goal of the planned research is to unveil the central neural mechanisms responsible for the altered control of the upper airway using rodent models. The studies will combine monitoring of upper airway muscle activity across the sleep-wake cycle in chronically instrumented rats with quantitative studies of gene and protein expression in brain regions responsible for the control of upper airways. To model the conditions similar to those in OSA patients, rodents will be subjected to manipulations such as sleep deprivation, exposures to alternating levels of oxygen and surgical interventions that increase the load on upper airway muscles.