For most animal brains, a steady supply of oxygen and glucose are essential to meet the high energy demands of neural circuit function. Aquarana catesbeiana, the American bullfrog, is unique in that it can repeatedly transition between hypoxia intolerant and tolerant states, a form of neural plasticity triggered during aquatic winter hibernation. This transitional ability allows the bullfrog to pause respiratory circuit activity for the winter months, then restart and sustain that activity as a prerequisite to resuming normal ventilation. Restarting a rhythmic circuit after months of inactivity is a metabolically demanding task and requires more energy than the frog can produce through oxidative phosphorylation in this breathless state, yet it does not suffer the lethal effects of neural energetic failure. 

While the exact mechanisms of this remarkable plasticity have yet to be fully described, pharmacological inhibition of α1-adrenoceptors has been found to reverse some of the hibernation-induced improvements in respiratory circuit activity during oxygen and glucose deprivation. Several types of adrenoceptors are well-established regulators of glycogenolysis in hepatic and muscle tissue. This receptor types has also been implicated in the glycogen metabolism of astrocytes, a glial cell type that supports energetic homeostasis in the brain. The largest source of neural noradrenaline, a structure called the locus coeruleus, has a well-characterized role as a chemosensor and increases signaling activity in hypercapnic conditions. This led me to explore whether the increased noradrenergic neuron signaling activity typically seen in response to hypercapnia is also triggered during oxygen and glucose deprivation, and if this response is altered by hibernation. Additionally, I tested if pharmacological inhibition of α1 noradrenergic receptors decreased the metabolic resistance seen in post-hibernation frogs by inhibiting astrocytic glycogenolysis and subsequent anaerobic glycolysis. 

Overall, the results of these experiments begin to uncover how alterations induced by hibernation in the neuromodulatory and neurometabolic systems may contribute to improving the energy status of neural tissues and the brain during metabolic limitation.