Metabolic signaling by lactate in the brain

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.