The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is an important determinant of CO2-H+ sensitivity during wakefulness. Bilateral, stainless steel microtubules were implanted into the CFN (N = 9) for injection (0.5–10 μl) of the neurotoxin ibotenic acid. Two or more weeks after implantation of the microtubules, eupneic breathing and CO2-H+ sensitivity did not differ significantly (P \u3e 0.10) from pre-implantation conditions. Injection of ibotenic acid (50 mM) did not significantly alter eupneic PaCO2 (P \u3e 0.10). The coefficient of variation of eupneic PaCO2 was 4.0 ± 0.6 and 3.7 ± 0.4% over the 2 weeks before and after the lesion, respectively. CO2-H+ sensitivity expressed as inspired ventilation/PaCO2 decreased from 2.15 ± 0.17 pre-lesion to 1.58 ± 0.26 l/(min mmHg) 3–6 days post-lesion (P \u3c 0.02, −27%). There was no significant (P \u3e 0.10) recovery of sensitivity between 7 and 10 days post-lesion. The lesion also increased (P \u3c 0.05) the day-to-day variability of this index by nearly 100%. When CO2 sensitivity was expressed as elevated inspired CO2/room air VI, values at 7%, but not 3 and 5% inspired CO2, were reduced and more variable (P \u3c 0.05) after the ibotenic acid injections. We conclude that during wakefulness, the CFN contributes relatively more to overall ventilatory drive at high relative to low levels of hypercapnia
