RATIONALE: Exogenous serotonin at the hypoglossal motor nucleus (HMN) stimulates genioglossus (GG) muscle activity. However, whether endogenous serotonin contributes to GG activation across natural sleep-wake states has not been determined, but is relevant given that serotonergic neurons have decreased activity in sleep and project to pharyngeal motoneurons. OBJECTIVES: To determine the role of endogenous serotonin at the HMN in modulating GG activity across natural sleep-wake states. METHODS: Ten rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm wires for respiratory muscle recordings. Microdialysis probes were implanted into the HMN for perfusion of artificial cerebrospinal fluid and the serotonin receptor antagonist mianserin (100 microM). MEASUREMENTS AND MAIN RESULTS: In room air, there was no effect of mianserin on respiratory-related or tonic GG activities across sleep-wake states (p > 0.300). In hypercapnia, however, the normal declines in GG activity from non-REM to REM sleep, and wakefulness to REM sleep, were reduced with mianserin (p < 0.005). These data demonstrate a normally low endogenous serotonergic drive modulating GG activity unless augmented by reflex inputs. We also demonstrated a significant serotonergic drive modulating GG activity in vagotomized rats, but not in vagi-intact rats, under anesthesia, suggesting that previous results in reduced preparations may have been influenced by vagotomy. CONCLUSIONS: The results show a minimal endogenous serotonergic drive at the HMN modulating GG activity across sleep-wake states, unless augmented by reflex inputs. This result has implications for pharmacologic strategies aiming to increase GG activity by manipulating endogenous serotonin in patients with obstructive sleep apnea.
RATIONALE: Exogenous serotonin at the hypoglossal motor nucleus (HMN) stimulates genioglossus (GG) muscle activity. However, whether endogenous serotonin contributes to GG activation across natural sleep-wake states has not been determined, but is relevant given that serotonergic neurons have decreased activity in sleep and project to pharyngeal motoneurons. OBJECTIVES: To determine the role of endogenous serotonin at the HMN in modulating GG activity across natural sleep-wake states. METHODS: Ten rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm wires for respiratory muscle recordings. Microdialysis probes were implanted into the HMN for perfusion of artificial cerebrospinal fluid and the serotonin receptor antagonist mianserin (100 microM). MEASUREMENTS AND MAIN RESULTS: In room air, there was no effect of mianserin on respiratory-related or tonic GG activities across sleep-wake states (p > 0.300). In hypercapnia, however, the normal declines in GG activity from non-REM to REM sleep, and wakefulness to REM sleep, were reduced with mianserin (p < 0.005). These data demonstrate a normally low endogenous serotonergic drive modulating GG activity unless augmented by reflex inputs. We also demonstrated a significant serotonergic drive modulating GG activity in vagotomized rats, but not in vagi-intact rats, under anesthesia, suggesting that previous results in reduced preparations may have been influenced by vagotomy. CONCLUSIONS: The results show a minimal endogenous serotonergic drive at the HMN modulating GG activity across sleep-wake states, unless augmented by reflex inputs. This result has implications for pharmacologic strategies aiming to increase GG activity by manipulating endogenous serotonin in patients with obstructive sleep apnea.
Authors: Luigi Taranto-Montemurro; Ludovico Messineo; Scott A Sands; Ali Azarbarzin; Melania Marques; Bradley A Edwards; Danny J Eckert; David P White; Andrew Wellman Journal: Am J Respir Crit Care Med Date: 2019-05-15 Impact factor: 21.405
Authors: Yu-Lun Lo; Amy S Jordan; Atul Malhotra; Andrew Wellman; Raphael A Heinzer; Matthias Eikermann; Karen Schory; Louise Dover; David P White Journal: Thorax Date: 2007-03-27 Impact factor: 9.139