Focal microdialysis of CO2 in the perifornical-hypothalamic area increases ventilation during wakefulness but not NREM sleep

We investigated whether the perifornical-lateral hypothalamic area (PF-LHA), where the orexin neurons reside, is a central chemoreceptor site by microdialysis of artificial cerebrospinal fluid (aCSF) equilibrated with 25% CO2 into PF-LHA in conscious rats. This treatment is known to produce a focal tissue acidification like that associated with a 6–7 mm Hg increase in arterial PCO2PCO2. Such focal acidification in the PF-LHA significantly increased ventilation up to 15% compared with microdialysis of normal aCSF equilibrated with 5% CO2 only in wakefulness but not in sleep in both the dark (P = 0.004) and light (P < 0.001) phases of the diurnal cycle. This response was predominantly due to a significant increase in respiratory frequency (11%, P < 0.001). There were no significant effects on ventilation in the group with probes misplaced outside the PF-LHA. These results suggest that PF-LHA functions as a central chemoreceptor site in the central nervous system in a vigilant state dependent manner with predominant effects in wakefulness.

► We focal acidified perifornical-lateral hypothalamic area (PF-LHA) by CO2/H+ in conscious rat.
► Focal acidification of PF-LHA significantly increased ventilation mainly due to breathing frequency.
► The enhanced ventilatory response was only observed in wakefulness not in sleep.
► Focal acidification of outside the PF-LHA had no effect on respiration.