Microdialysis perfusion of 5-HT into hypoglossal motor nucleus differentially modulates genioglossus activity across natural sleep-wake states in rats

1. Serotonin (5-hydroxytryptamine, 5-HT) excites hypoglossal (XII) motoneur ons in reduced preparations, and it has been suggested that withdrawal of 5 -HT may underlie reduced genioglossus (GG) muscle activity in sleep. Howeve r, systemic administration of 5-HT agents in humans has limited effects on GG activity. Whether 5-HT applied directly to the XII motor nucleus increas es GG activity in an intact preparation either awake or asleep has not been tested. 2. The aim of this study was to develop a novel freely behaving animal mode l for in vivo microdialysis of the XII motor nucleus across sleep-wake stat es, and test the hypothesis that 5-HT application will increase GG activity . 3. Eighteen rats were implanted with electroencephalogram and neck muscle e lectrodes to record sleep-wake states, and G G; and diaphragm electrodes fo r respiratory muscle recording. Microdialysis probes were implanted into th e XII motor nucleus and perfused with artificial cerebrospinal fluid (ACSF) or 10 mM 5-HT. 4. Normal decreases in GG activity occurred from wakefulness to non-rapid e ye movement (non-REM) and REM sleep with ACSP (P < 0.01). Compared to ACSF, 5-HT caused marked GG activation across all sleep-wake states (increases o f 91-251%, P < 0.015). Importantly, 5-HT increased sleeping GG activity to normal waking levels for as long as 5-HT was applied (3-5 h). Despite tonic stimulation by 5-HT, periods of phasic GG suppression and excitation occur red in REM sleep compared with non-REM. 5. The results show that sleep-wake states differentially modulate GG respo nses to 5-HT at the,XII motor nucleus. This animal model using in vivo micr odialysis of the caudal medulla will enable the determination of neural mec hanisms underlying pharyngeal motor control in natural sleep.