Breathing Frequency (fR) Is No Longer Under Chemoreflex Control During REM Sleep

Abstract

ObjectiveTo define the contribution of central chemoreception in general and the retrotrapezoid nucleus (RTN) in particular to the regulation of breathing in REM sleep. MethodsEEG, neck EMG, blood pressure, fR and tidal volume (VT) were recorded in 23 conscious adult male Sprague‐Dawley rats. RTN was optogenetically stimulated with channelrhodopsin‐2 (ChR2, 20s) or inhibited with archaerhodopsin (Arch; 10 s) during natural sleep and quiet wake periods. ChR2 and Arch were delivered using previously described PRSX8‐promoter containing lentiviral vectors. Main ResultsIn quiet wake or non‐REM sleep, hypercapnia (3 or 6% FiCO2) increased both fR and VT; in REM sleep, hypercapnia increased VT but fR was unaffected. Optogenetic inhibition of RTN neurons reduced VT in all three states but reduced fR only during quiet wake and non‐REM sleep. Optogenetic stimulation of RTN neurons always increased VT but raised fR only in quiet wake and non‐REM sleep. Phasic stimulation of RTN at frequencies above resting fR entrained and shortened the breathing cycle except in REM sleep. Phasic RTN stimulation produced active expiration only during wake and increased fR exclusively by reducing the duration of the post‐inspiratory phase.ConclusionsDuring REM sleep, VT regulation by both hypercarbia and RTN is retained but the overall hypercapnic ventilatory reflex is reduced because fR is no longer under chemoreceptor control. Furthermore, respiratory drive contributed by RTN is remarkably state‐dependent, active expiration being elicited only during wake and tachypnea only during non‐REM sleep and quiet wake. Support: HL074011.