Circadian dependence of receptors that mediate wake-related excitatory drive to hypoglossal motoneurons☆

Abstract Serotonin (5-HT), norepinephrine and orexins (ORX) are the three best established mediators of wake-related activation of hypoglossal (XII) motoneurons that innervate the muscles of the tongue. Since the tongue's use is temporarily closely aligned with the rest–activity cycle, we tested whether expression of mRNA for relevant 5-HT, norepinephrine and ORX receptors varies in the XII nucleus with the rest–activity cycle. Adult rats ( n  = 7–9/group) were decapitated at 8–9 am (near rest period onset) or at 6–7 pm (near active period onset). Tissue micropunches were extracted from medullary slices containing the XII motor and sensory external cuneate (ECN) nuclei. 5-HT 2A , α 1 -adrenergic and ORX type 2 receptor mRNAs were quantified using RT-PCR. Only 5-HT 2A receptor mRNA levels differed between the two time points and were higher at the active period onset; no differences were detected in the ECN. Consistent with the mRNA results, 5-HT 2A protein levels were also higher in the XII nucleus at the active period onset than at rest onset. Thus, the endogenous serotonergic excitatory drive to XII motoneurons may be enhanced through circadian- or activity-dependent mechanisms that increase the availability of 5-HT 2A receptors prior to the active period. Conversely, reduced levels of 5-HT 2A receptors during the rest–sleep period may exacerbate the propensity for sleep-disordered breathing in subjects with anatomically compromised upper airway.