Brain function has high energy demands, and when these needs are not met there is a loss of neural function. Most of the energy for brain function comes from burning sugar (glucose) using oxygen. In contrast, preliminary observations led to discovery of an alternate scenario whereby bullfrogs display an unusually large ability to abandon these conventional energy sources to promote survival. Like most vertebrates, brain activity in frogs typically requires energy from glucose metabolism. However, hibernation transforms the bullfrog brain to function for over two hours without glucose and oxygen, promoting survival when these resources are otherwise limited. This represents the largest improvement in neural activity during severe metabolic stress reported in the vertebrate brain. This project tests the hypothesis that this impressive feat involves the metabolism of by-products of fat breakdown (ketone bodies) without any ongoing glucose metabolism. While ketone bodies are well-known to fuel the brain during starvation and certain diets, neural function in most animals requires at least some glucose at the same time. As issues with glucose metabolism contribute to diverse neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and ALS, these studies have long-term implications for improving brain function in neurodegenerative diseases of metabolic origin. This project will also train graduate students, including introducing a pipeline for education training