Frogs uncouple neural activity from oxygen consumption after hibernation

Brain activity is costly, and aerobic metabolism supplies ~90% of the ATP for cellular and synaptic function. Accordingly, oxygen consumption varies to match activity demands of neural circuits, and mitochondrial defects that reduce aerobic metabolism cause various neurological disorders. Brain activity in frogs has energy demands typical of an average vertebrate, but surprisingly, improves function upon stopping oxidative metabolism from a few minutes to hours following hibernation. While this represents a large capacity to shift to glycolysis as a lone ATP source in an adult brain circuit, we hypothesized activity's reliance on oxygen may be globally reduced. We tested this by simultaneously assessing tissue oxygen consumption and neural activity from a brainstem motor network. We show that hibernation triggers a reduction in the oxygen consumed by neural activity and activity-independent mitochondrial respiration. In accordance with lower aerobic requirements, network output remained stable over a wide range of tissue oxygen levels, from baseline to anoxia, whereas controls were disrupted by moderate hypoxia. Despite operating with reduced aerobic metabolism, network activity was similar to controls, and activity increases did not accelerate oxygen consumption until seizure-like bursts ensued. Therefore, circuits in the vertebrate brain have the surprising capacity to uphold normal network functions with reduced aerobic metabolism. These findings introduce low-cost states can lie dormant within otherwise energetically expensive circuits and raise the question why costly designs are the default when they, in some cases, may be unnecessary and predispose organisms to metabolic pathologies.