Frogs Uncouple Neural Activity From Oxygen Consumption After Hibernation

ABSTRACT Aim Aerobic metabolism supplies ~90% of the ATP for neural activity. In frogs, activity has large aerobic needs typical of an average vertebrate, but surprisingly, can shift to using only glycolysis upon emergence from hibernation. We hypothesized that hibernation triggers a global reduction in the aerobic cost of neural function. Methods We simultaneously measured activity of the brainstem respiratory network via motor nerves and tissue O 2 partial pressure (pO 2 ) in vitro from control and hibernated bullfrogs (4 weeks cold submergence; 4°C). To identify which functions differentially consume O 2 , we sequentially blocked activity and various cellular processes requiring activity‐independent ion regulation and used the resulting tissue pO 2 change (ΔpO 2 ) as an index of O 2 consumed. We further assessed how activity varies as a function of tissue pO 2 and how O 2 consumption varies across network activity levels. Results Despite similar network activity levels, we provide three lines of evidence that hibernation reduces its aerobic requirement. First, hibernators consume less O 2 for baseline activity. Second, network output remains stable from baseline to anoxia, whereas moderate hypoxia disrupts controls. Finally, accelerating activity does not enhance O 2 consumption as in controls, but aerobic metabolism ultimately increases during seizure‐like activity. Conclusion Hibernating frogs reduce aerobic needs for sustaining physiological levels of neural activity, revealing how they overcome the challenge of restarting motor circuits on the background of hypoxia during emergence from hibernation. More broadly, vertebrate neural circuits seemingly constrained by aerobic metabolism can exhibit substantial plasticity in the aerobic requirements for function.