Frogs uncouple neural activity from oxygen consumption after hibernation

Abstract

AimAerobic 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. MethodsWe simultaneously measured activity of the brainstem respiratory network via motor nerves and tissue oxygen partial pressure (pO2) in vitro from control and hibernated bullfrogs (4 weeks cold submergence; 4{degrees}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 ({Delta}pO2) 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. ResultsDespite similar network activity levels, we provide three lines of evidence that hibernation reduces its aerobic requirement. First, hibernators consume less oxygen for baseline activity. Second, network output remains stable from baseline to anoxia, while moderate hypoxia disrupts controls. Finally, accelerating activity does not enhance oxygen consumption as in controls, but aerobic metabolism ultimately increases during seizure-like activity. ConclusionHibernating 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. Practitioner pointsO_LIHibernation in bullfrogs reduces the oxygen consumed by neural activity while maintaining normal network output, demonstrating that the aerobic requirements of brain function are not fixed in the vertebrate brain. C_LIO_LIAfter hibernation, brainstem motor circuits maintain stable function from high levels of O2 to anoxia and do not increase O2 consumption when activity is elevated within the physiological range. C_LIO_LIThese findings reveal that vertebrate neural circuits can enter metabolic states requiring far less aerobic respiration, which may inform strategies for improving metabolic resilience in the brain during conditions of impaired oxygen delivery and other metabolic dysfunction. C_LI