CO₂ microdialysis in retrotrapezoid nucleus of the rat increases breathing in wakefulness but not in sleep

Central chemoreceptors are widespread within the brain stem. We suggest that their function at some sites may vary with the state of arousal. In this study, we tested the hypothesis that the function of chemoreceptors in the retrotrapezoid nucleus (RTN) varies with sleep and wakefulness. In unanesthetized rats, we produced focal acidification of the RTN by means of a microdialysis probe (tip containing the semipermeable membrane = 1-mm length, 240-μm diameter, and 45-nl volume). With the use of a dialysate equilibrated with 25% CO₂, the tissue pH change (measured in anesthetized animals) was1) limited to within 550 μm of the probe and, 2) at the probe tip, was equivalent to that observed with end-tidal$P{\text{CO}}_2$ of 63 Torr. This focal acidification of the RTN increased ventilation significantly by 24% above baseline, on average, in 13 trials in seven rats only during wakefulness. The effect was entirely due to an increase in tidal volume. During sleep defined by behavioral criteria, ventilation was unaffected, on average, in 10 trials in seven rats. During sleep, the chemoreceptors in the RTN appear to be inactive, or, if active, the respiratory control system either is not responding or is responding with very low gain. Because ventilation is increased during sleep with all central chemoreceptor sites stimulated via systemic CO₂ application, other central chemoreceptor locations must have enhanced effectiveness.