Transforming neural activity to operate without glucose metabolism using brain-derived ketone bodies

The vertebrate brain is exquisitely sensitive to disruptions in glucose metabolism, and failure of adequate glucose delivery causes neurological dysfunction. Here, we discovered an animal with the capacity to defy this rule: We show that neural activity in frogs, animals with seemingly typical glucose demands, can stop metabolizing glucose by, in part, shifting to ketone bodies made exclusively within the brain after emergence from hibernation. This involves ketone body synthesis and transport from astrocytes to neurons to power synaptic transmission, along with the upregulation of gene expression that controls fatty acid catabolism and ketone body transport. Brain-derived ketone bodies also