Synaptic rearrangement of NMDA receptors controls memory engram formation and malleability in the cortex | Science Advances

Initially hippocampal dependent, memory representations rely on a broadly distributed cortical network as they mature over time. How these cortical engrams acquire stability during systems-level memory consolidation without compromising their dynamic nature remains unclear. We identified a highly responsive “consolidation switch” in the synaptic composition of N -methyl- d -aspartate receptors (NMDARs), which dictates the progressive embedding and persistence of enduring memories in the rat cortex. Cortical GluN2B subunit–containing NMDARs were preferentially recruited upon encoding of associative olfactory memory to support neuronal allocation of memory engrams. As consolidation proceeds, a learning-induced redistribution of GluN2B subunit–containing NMDARs outward synapses increased synaptic GluN2A subunit contribution and enabled stabilization of remote memories. In contrast, synaptic reincorporation of GluN2B subunits occurred during subsequent forgetting. By manipulating the surface distribution of GluN2A and GluN2B subunit–containing NMDARs at cortical synapses, we uncovered that the rearrangement of GluN2B-containing NMDARs constitutes an essential tuning mechanism that determines the fate of cortical memory engrams and controls their malleability.