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 O₂ partial pressure (pO₂) in vitro from control and hibernated bullfrogs (4 weeks cold submergence; 4°C). To identify which functions differentially consume O₂, we sequentially blocked activity and various cellular processes requiring activity-independent ion regulation and used the resulting tissue pO₂ change (ΔpO₂) as an index of O₂ consumed. We further assessed how activity varies as a function of tissue pO₂ and how O₂ 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 O₂ for baseline activity. Second, network output remains stable from baseline to anoxia, whereas moderate hypoxia disrupts controls. Finally, accelerating activity does not enhance O₂ 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.