Chemogenetic modulation of the parafacial respiratory group influences the recruitment of abdominal activity during REM sleep

Abstract

Current theories on respiratory control postulate that the respiratory rhythm is generated by oscillatory networks in the medulla: preBötzinger complex (preBötC) is the master oscillator responsible for generating inspiration, while parafacial respiratory group (pFRG) drives active expiration through recruitment of expiratory abdominal (ABD) muscle activity. Research addressing the role of pFRG in ventilation and rhythm generation across sleep states is limited. We recently reported the occurrence of ABD recruitment occurring despite the induction of muscle paralysis during REM sleep. This ABD recruitment was associated with increased tidal volume and regularization of the respiratory period in rats. As pFRG generates active expiration through the engagement of ABD muscles, we hypothesized that the expiratory oscillator is also responsible for the ABD recruitment observed during REM sleep. To test this hypothesis, we inhibited and activated pFRG using chemogenetics (i.e. designer receptors exclusively activated by designer drugs) while recording EEG and respiratory muscle EMG activities across sleep-wake cycles in male Sprague-Dawley rats. Our results suggest that inhibition of pFRG reduced the number of REM events expressing ABD recruitment, in addition to the intensity and prevalence of these events. Conversely, activation of pFRG resulted in an increase in the number of REM events in which ABD recruitment was observed, as well as the intensity and prevalence of ABD recruitment. Interestingly, modulation of pFRG activity did not affect ABD recruitment during NREM sleep or wakefulness. These results suggest that the occurrence of ABD recruitment during sleep is dependent on pFRG activity and is state dependent.

Keywords: REM sleep; abdominal recruitment; expiration; modulation; parafacial respiratory group; respiratory control; sleep; vigilance states.