Genetic depletion of 5-HT increases central apnea frequency and duration and dampens arousal but does not impact the circadian modulation of these variables

Abstract

We examined the impact of serotonin (5-HT) on the frequency and duration of central apneic events and the frequency of accompanying arousals during nonrapid and rapid eye movement (NREM and REM, respectively) sleep across the light/dark cycle. Electroencephalography, electromyography, core body temperature, and activity were recorded for 24 h following implantation of telemeters in wild-type (Tph2^+/+) and tryptophan hydroxylase 2 knockout (Tph2^-/-) male mice. The frequency and duration of central apneic events were increased, the number of apneic events coupled to an arousal was decreased, and the ventilatory sensitivity to hypoxia and hypercapnia was decreased in the Tph2^-/- compared with the Tph2^+/+ mice during NREM sleep. Apnea frequency and duration were similar in the Tph2^-/- and Tph2^+/+ mice during REM sleep. The duration of apneic events during REM compared with NREM sleep was similar in the Tph2^-/- mice. In contrast, the duration was greater during REM sleep in the Tph2^+/+ mice. Our results also revealed that apnea frequency was greater during the light compared with the dark cycle. Circadian modulation of this variable was evident in both the Tph2^-/- and Tph2^+/+ mice during NREM and REM sleep. We conclude that depletion of 5-HT increases the frequency and duration of central apneic events, dampens arousal, and blunts the ventilatory response to hypoxia and hypercapnia during NREM sleep but is not essential for the circadian modulation of these variables. NEW & NOTEWORTHY The presence of serotonin (5-HT) in the central nervous system diminishes the frequency of central apneic events. This neuromodulator also moderates the duration of central apneic events and promotes arousal from central events if they occur during nonrapid eye movement (NREM) sleep. However, 5-HT is not responsible for the circadian modulation of apnea frequency, which we found was greater during NREM sleep in the light compared with the dark cycle.

Keywords: arousal; diaphragm muscle activity; nonrapid eye movement sleep; telemetry.