Neurons in Need: Glucose, but Not Lactate, Is Required to Support Energy-Demanding Synaptic Transmission

The brain derives its energy from a combination of several metabolic substrates. The principal energy substrate of the brain is glucose, but the metabolic role of cerebral lactate has been debated for decades. In particular, the hypothesis that astrocyte-derived lactate is needed to fuel neuronal metabolism during activation remains a heated topic. This Editorial highlights a study in the current issue of Journal of Neurochemistry exploring the metabolic relationship between glucose and lactate metabolism in sustaining neuronal network signaling. The study by Söder et al. demonstrates that neurons are only able to sustain energy-demanding synchronized synaptic transmission when glucose is freely available. Blocking lactate transport had no effect on neuronal signaling when glucose was present, highlighting that any potential transfer of lactate is not required during high neuronal workload. In fact, when lactate was supplied as the primary fuel, neurons were unable to sustain synchronized signaling. Using a lactate biosensor, the authors further show that neurons produce and release lactate, both during resting and stimulated conditions. As synchronized synaptic transmission underlies higher brain function, this paper underscores the absolute necessity of neuronal glucose metabolism to maintain brain function.