Graded reductions in oxygenation evoke graded reconfiguration of the isolated respiratory network

Neurons depend on aerobic metabolism, yet are very sensitive to oxidative stress and, as a consequence, typically operate in a low O(2) environment. The balance between blood flow and metabolic activity, both of which can vary spatially and dynamically, suggests that local O(2) availability markedly influences network output. Yet the understanding of the underlying O(2)-sensing mechanisms is limited. Are network responses regulated by discrete O(2)-sensing mechanisms or, rather, are they the consequence of inherent O(2) sensitivities of mechanisms that generate the network activity? We hypothesized that a broad range of O(2) tensions progressively modulates network activity of the pre-Bötzinger complex (preBötC), a neuronal network critical to the central control of breathing. Rhythmogenesis was measured from the preBötC in transverse neonatal mouse brain stem slices that were exposed to graded reductions in O(2) between 0 and 95% O(2), producing tissue oxygenation values ranging from 20 ± 18 (mean ± SE) to 440 ± 56 Torr at the slice surface, respectively. The response of the preBötC to graded changes in O(2) is progressive for some metrics and abrupt for others, suggesting that different aspects of the respiratory network have different sensitivities to O(2).