Figure 4. RTN activates multiple breathing parameters in a state‐dependent fashion.

A, unilateral phasic optogenetic activation of RTN (channelrhodopsin‐2; trains of 3 light pulses; trains delivered at a rate slightly above resting breathing frequency) during quiet waking entrains the respiratory pattern generator, increases inspiratory amplitude, produces active expiration (note the distinctive peak‐expiratory flow, PEF, during late expiratory phase, E2) and activates the expiratory brake (note reduced expiratory flow during early expiration, E1). During non‐REM sleep (same rat), RTN activation still entrained the pattern generator and increased inspiratory amplitude but active expiration and the expiratory brake were no longer elicited (from Burke et al. 2015, with slight modifications). B, bilateral optogenetic inhibition of RTN (archaerhodopsin, 10 s light pulses; green bars) reduces respiratory frequency (f _R) and tidal volume (V _T) during quiet resting and non‐REM sleep. During REM sleep RTN inhibition has no effect on f _R but still reduces V _T, albeit to a lesser degree. This evidence indicates that RTN controls breathing frequency only when the pattern generator is auto‐rhythmic (slow wave sleep or quiet awake state) but not when it is externally driven, as in REM sleep. Adapted from Basting et al. 2015). C, schematic representation of the four known effects of RTN on breathing and their differential regulation by the state of vigilance.