Plasticity in the central neural control of the upper airway

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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.