Noradrenergic Signaling Appears to Increase in Response to Hypoxia and Hypoglycemia in<i>Aquarana catesbeiana</i>Locus Coeruleus Neurons

Most animal brains require a consistent supply of oxygen and glucose to function. Aquarana catesbeiana, the American bullfrog, displays neural plasticity in response to oxygen and glucose deprivation (OGD), increasing the organism’s capacity to function by ~thirty-fold after hibernation; this is the greatest improvement documented in vertebrate animals. We hypothesized that noradrenergic signaling contributes to this response. To test this hypothesis, we applied inhibitors of adrenergic receptors α1, α2, and β. None of these antagonists influenced responses to simulated ischemia (oxygen and glucose deprivation; OGD) in control, warm-acclimated animals. However, after hibernation, inhibition of α1-adrenoceptors reverses some of the improvements in activity during the early phase of OGD (naïve control (n=7) vs. 500 nM prazosine (n=6); p=0.004; time to slow to 10% of baseline frequency). This led us to address whether hibernation causes noradrenergic neurons to alter their rate of activity during OGD, which would activate α1 receptors, improving overall robustness during ischemia after hibernation. Locus coeruleus neurons of amphibians are primarily responsible for noradrenergic signaling in the frog brain. Therefore, we used whole-cell patch clamp electrophysiology in bullfrog brain tissue slices to determine neuron action potential firing response to OGD. Recordings on a control (non-hibernating) population of 40 locus coeruleus neurons show that on average, the control cells do not demonstrate a significant difference in firing rate in response to OGD (p=0.3015; Holm-Sidak’s multiple comparisons test. Initial experiments on ten cold (hibernating) locus coeruleus neurons taken from frogs held at 4º C for a minimum of thirty days before data collection to induce hibernation indicate that firing rate increases significantly during ODG (p= 0.0002; Holm-Sidak’s multiple comparisons test). Therefore, noradrenergic LC neurons from hibernators display increases in firing rate during OGD, which appears to act at α1 to promote activity. Future work will address the neuronal or metabolic mechanisms through which norepinephrine acts at α1 receptors. Overall, these results begin to uncover how alterations induced by hibernation in the neuromodulatory system may contribute to improving the energy status of neural tissues and the brain during energy limitations. National Institutes of Health Grant R01 NS114514; University of Missouri - Division of Biological Sciences. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.