Noradrenergic A7 neurons and Upper Airway Motor Control

Brentwood Biomedical Research Institute, Los Angeles CA

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Abstract

DESCRIPTION (provided by applicant): Obstructive Sleep Apnea (OSA) is a growing health problem which affects almost 5% of the adult population. Due to airway obstruction and repetitive waking during sleep, OSA patients have excessive daytime sleepiness and a diminished quality of life. OSA is associated with hypertension, diabetes, coronary artery disease, strokes and congestive heart failure. The treatment options for OSA are limited to surgery and the use of oral appliances; no effective pharmacological therapy is available. Hypoglossal motoneurons play a critical role in pathology of the OSA because they innervate the muscles of the tongue that are important for maintaining airway patency. A decrease in their activity during sleep and especially rapid eye movement (REM) sleep is the main cause of airway obstruction in OSA. Therefore, complete understanding of the neuronal network that controls activity of hypoglossal motoneurons during sleep and wakefulness may help to develop pharmacological strategies to treat OSA. In the proposed project, we will study the role of noradrenergic A7 neurons in the neuronal network that controls activity of hypoglossal motoneurons during the natural sleep-wake cycle using a novel animal model. We will obtain data regarding behavior of A7 neurons during states of sleep and wakefulness, their downstream projections and their contribution to the mechanisms of the depression of hypoglossal motoneurons excitability during non-REM and REM sleep. Obtained information will advance our understanding of the neuronal network and neurochemical mechanisms that control state-dependent activity of hypoglossal motoneurons and provide a foundation for developing effective pharmacological treatments for OSA