Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

The transfer of lactate, a product of aerobic glycolysis, from astrocytes to neurons was recently shown to be necessary for the establishment of long-term memory and for the maintenance of in vivo long-term potentiation. Here, we report that lactate induces the expression of plasticity genes such as Arc, c-Fos, and Zif268 in neurons. The action of lactate is mediated by the modulation of NMDA receptor activity and the downstream Erk1/2 signaling cascade, through a mechanism associated with changes in the cellular redox state. These observations unveil an unexpected role of lactate as a signaling molecule in addition to its role in energy metabolism and open a previously unidentified research avenue for the study of neuronal plasticity and memory.