NMDA and AMPA receptors: old channels, new tricks

Learning and memory depend on persistent changes in synaptic strength that require neuronal gene expression. An unresolved question concerns the mechanisms by which activity at synapses is transduced into a nuclear transcriptional response. In the prevailing view, N-methyl-d-aspartate (NMDA)- and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors have distinct roles in controlling synaptic strength: AMPA receptors effect short-term changes in synaptic strength, whereas NMDA receptors regulate genes that are required for the long-term maintenance of these changes. Here, we review recent data on the roles of these two types of receptor in activity-dependent gene expression. We discuss evidence that signals from NMDA receptors and AMPA receptors are integrated to specify transcriptional responses for particular plasticity related genes.