Selected Contribution: Effects of sleep-wake state on the genioglossus vs. diaphragm muscle responses to CO₂ in rats

Abstract

The effects of sleep on the ventilatory responses to hypercapnia have been well described in animals and in humans. In contrast, there is little information for genioglossus (GG) responses to a range of CO(2) stimuli across all sleep-wake states. Given the notion that sleep, especially rapid eye movement (REM) sleep, may cause greater suppression of muscles with both respiratory and nonrespiratory functions, this study tests the hypothesis that GG activity will be differentially affected by sleep-wake states with major suppression in REM sleep despite excitation by CO(2). Seven rats were chronically implanted with electroencephalogram, neck, GG, and diaphragm electrodes, and responses to 0, 1, 3, 5, 7, and 9% CO(2) were recorded. Diaphragm activity and respiratory rate increased with CO(2) (P < 0.001) across sleep-wake states with significant increases at 3-5% CO(2) compared with 0% CO(2) controls (P < 0.05). Phasic GG activity also increased in hypercapnia but required higher CO(2) (7-9%) for significant activation (P < 0.05). Further studies in 15 urethane-anesthetized rats with the vagi intact (n = 6) and cut (n = 9) showed that intact vagi delayed GG recruitment with hypercapnia but did not affect diaphragm responses. In the naturally sleeping rats, we also showed that GG activity was significantly reduced in non-REM and REM sleep (P < 0.04) and was almost abolished in REM even with stimulation by 9% CO(2) (decrease = 80.4% vs. wakefulness). Such major suppression of GG activity in REM, even with significant respiratory stimulation, may explain why obstructive apneas are more common in REM sleep.

State-Dependent Modulation of Breathing in Urethane-Anesthetized Rats

“…Similar to previous results in natural sleep (Megirian et al, 1985;Horner et al, 2002), we observed strong CO 2 -mediated potentiation of GG EMG activity in nREM-like epochs, but limited effects during REM-like epochs, suggesting that EMG potentiation is still present under urethane anesthesia and is still state dependent. ABD EMG activity was also potentiated during CO 2 stimulation, consistent with previous reports (Iizuka and Fregosi, 2007;Marina et al, 2010;Abbott et al, 2011).…”

“…Mild hypoxia potently increased respiratory frequency across states and decreased the time spent in nREM-like sleep, similar to natural sleep (Pappenheimer, 1977;Horner et al, 2002). Relative differences among states were maintained (higher respiratory and sigh rates, tidal volume, minute ventilation in REM-like state).…”

“…The magnitude of the depression in GG EMG activity during sleep (Jelev et al, 2001;Sood et al, 2005;Horner, 2008a;Lu and Kubin, 2009) depends strongly on posture, vestibular inputs, and state-dependent neuromodulators (Megirian et al, 1985;Rossiter and Yates, 1996;Horner et al, 2002;Horner, 2008b). Our results suggest that urethane anesthesia does not interfere with the neuromodulatory processes controlling GG muscular activity, at the level of either the motoneuron or premotoneuron networks that determine muscle activity.…”

“…It is proposed that, compared with wakefulness, chemosensitivity is depressed in nREM and further depressed in REM sleep (Douglas, 2005). However, experimental data are limited because of the brevity of REM epochs in natural sleep and the tendency for chemosensory stimuli (hypoxia or hypercapnia) to cause arousal (Horner et al, 2002;Nattie, 2006, 2010). In our experiments, we observed a stronger hypercapnic ventilatory response in nREM-like compared with REM-like epochs, but these differences were not dramatic.…”

Neural Control of Respiration by the Retrotrapezoid Nucleus.

“…For example, although the respiratory chemoreflexes still operate during REM sleep, the breathing frequency (f R ) is typically unaffected by hypoxia or hypercapnia (Coote, 1982;Berthon-Jones & Sullivan, 1984;Horner et al, 2002;Lovering et al, 2003;Nakamura et al, 2007). Also, in conscious cats ventilated to apnea during non-REM sleep, diaphragmatic EMG reemerges during REM sleep (Orem et al, 2005).…”