Neurons in the caudal nucleus tractus solitarius and dorsal motor nucleus of vagus (caudal solitary complex, cSC) are one of several sites of CO2-chemoreception in the mammalian brain (1). Our previous electrophysiology studies (in vitro) reveal that cSC neurons, particularly CO2/H+-sensitive neurons, are stimulated by hyperoxia and chemical oxidants (2, 3). These findings suggest that CO2-sensitive neurons employ redox and nitrosative signaling mechanisms. In this study, we have tested the hypothesis that CO2-sensitivity in cSC neurons increases with increasing pO2 based on changes in firing rate (△FR, impulses/second = imp/s). A brain slice/intracellular recording (ICR) station was adapted for use inside a hyperbaric chamber so that pO2 could be increased from 0.4 atmospheres absolute (ATA) to 1.95 ATA. Brain slices (400 μm) containing the cSC were harvested from Sprague-Dawley rats (aged P10-P42, both sexes) using methods approved by the USF Institutional Animal Care & Use Committee. ICRs (90-150 MΩ, 3 M K+ acetate) were initiated in cSC neurons in brain slices submerged in artificial cerebral spinal fluid (aCSF; 35-37°C) aerated with (in ATA) 0.4 O2, 0.05 CO2 & 0.55 N2 overlain by an atmosphere of 100% helium (He) pressurized to 2 ATA. aCSF was delivered at 2.5 mL/min using an HPLC pump. Hyperoxia was tested by switching to aCSF aerated with 0.9-0.95 or 1.9-1.95 O2 while HA was tested using 0.1 CO2. Table 1 reports FR responses measured in neurons at various levels of O2 & CO2 dissolved in aCSF at 2 ATA He. The trend was for CO2-chemosensitivity to increase with increasing pO2 with significance at the highest level of O2 tested. These findings suggest that oxidative stimuli, including hyperoxia and potentially redox stress, increase cellular CO2-chemosensitivity and, presumably, the magnitude of the hypercapnic ventilatory response. Parallel, ongoing studies of cSC neurons using fluorescence imaging in rat brain slices indicate that hyperoxia increases various reactive species, including singlet oxygen (4), superoxide, nitric oxide, peroxynitrite, hydrogen peroxide, hydroxyl radical, nitrogen dioxide and carbonate radicals (5). Which reactive species modulate neuronal CO2-sensitivity in the cSC during hypercapnic hyperoxia has yet to be determined.