Hypoglossal motoneurons are endogenously activated by serotonin during the active period of circadian cycle

Abstract

In obstructive sleep apnea patients, contraction of lingual muscles protects the pharyngeal airway from collapse. Hypoglossal (XII) motoneurons innervate the muscles of the tongue and are themselves under wake-related excitatory drives, including that mediated by serotonin (5-HT). Estimates of endogenous 5-HT activation vary among different studies. We tested whether endogenous drive mediated by 5-HT is present in rat XII motoneurons when measured during the active period of the circadian cycle. We monitored sleep-wake states and lingual and nuchal electromyograms (EMGs) while perfusing the XII nucleus with a vehicle or a 5-HT₂ receptor antagonist (mianserin, 0.2mM) at the active period onset. EMG levels were measured during each behavioral state and normalized by the mean EMG activity during wakefulness at 4-7am. Wake-related lingual EMG was significantly lower during mianserin perfusion than with the vehicle (53.0±9.7% vs. 84.5±8.7%; p=0.002). Mianserin had no effect on nuchal EMG or sleep-wake behavior. Thus, rat XII motoneurons receive endogenous serotonergic activation during wakefulness when measured during the dark period. This indicates that XII motoneuronal activity is enhanced by 5-HT output during the active period of the circadian cycle.

Keywords: Mianserin; Serotonin receptors; Sleep; Sleep apnea; Tongue; Upper airway.