Fueling Brain Inhibition: Integrating GABAergic Neurotransmission and Energy Metabolism

Despite decades of research in brain energy metabolism and to what extent different cell types utilize distinct substrates for their energy metabolism, this topic remains a vibrant area of neuroscience research. In this review, we focus on the substrates utilized by the inhibitory GABAergic neurons, which has been less explored than glutamatergic neurons. First, we discuss how GABAergic neurons may utilize both glucose, lactate, or ketone bodies under different functional conditions, and provide some preliminary data suggesting that unlike glutamatergic neurons, GABAergic neurons work well when substrate supply is restricted to lactate. We end by discussing the role of GABAergic neuron energy metabolism in pathologies where failure of inhibitory function play a central role, namely epilepsy, hepatic encephalopathy, and Alzheimer's disease.