Hypercapnic and hypoxic responses require intact neural transmission from the pre-Bötzinger complex

The central respiratory network that includes the pre-Bötzinger complex (pre-BötC), a region believed to contain rhythmogenic neurons, is capable of responding to fluctuations in CO₂ and pH. However, the role of inputs from this site in mediating ventilatory responses to hypercapnia and/or hypoxia in nonsedated animals is not well established. Therefore, in the present study we tested the hypothesis that altered transmission from the pre-BötC to its target sites would decrease chemosensory responsiveness to acute hypercapnia and modulate the ventilatory response to hypoxia. Colchicine was used to block axonal transport. At 48 h after bilateral microinjections of colchicine into the pre-BötC (100 μg/uL, 100 nL/site), but not saline, the baseline frequency of breathing decreased; however, rhythmicity was not altered. In addition, there was a significant fall in the ventilatory response to hypercapnia (5 and 12% CO₂) and hypoxia (8% O₂). These findings indicate that, inputs from pre-BötC neurons are of critical importance in providing the normal ventilatory response to both hypercapnia and hypoxia.