Lactate is known as an energy substrate for neurons. It is also emerging as a trophic signaling molecule regulating higher brain functions such as learning and memory. Lactate was shown to potentiate NMDA receptor signaling and regulate gene expression related to synaptic plasticity. Using patch-clamp recordings in cultured cortical neurons, we found that lactate enhanced amplitude and inactivation time-constant (tau) of NMDA receptor currents (INMDA) evoked by brief applications of glutamate and glycine. The effect on the amplitude was prevented by pre-treating neurons with a MCTs blocker or by including CaMKII inhibitors in the patch pipette, whereas the effect on tau was not.