Metabolic signaling by lactate in the brain

•Synaptic activity is accompanied by a transient rise in brain tissue lactate concentration.•The rise in lactate is explained by acute stimulation of glycolysis in astrocytes, mediated by neuronal release of K+ and glutamate.•Lactate serves as metabolic fuel for active neurons.•Lactate diffuses beyond the active zone, helping to recruit metabolic resources from resting areas and modulating higher-order brain functions.

High-resolution molecular and imaging techniques are shedding light on the mechanisms and functional significance of the transient rise in tissue lactate that accompanies synaptic activity. Despite high energy needs, neurons have a truncated glycolytic pathway that favors antioxidation over energy production, whereas astrocytes team up with oligodendrocytes to extract glucose from the blood, mobilize glycogen, and release lactate under neuronal command. Lactate energizes neurons but also diffuses beyond the active zone and modifies the activity of neurons and astrocytes in neighboring regions. Involved in a hierarchy of processes from neurovascular coupling to memory formation, lactate has a dual role as metabolic fuel and an intercellular messenger.