Differential roles of NR2A and NR2B subtypes in NMDA receptor-dependent protein synthesis in dendrites

Protein synthesis in dendrites is critical for long-term synaptic plasticity. Previous studies have identified an essential role of NMDA receptors in control of activity-dependent dendritic protein synthesis, but the contribution of NR2A- and NR2B-containing NMDA receptors, the two predominant subtypes of NMDA receptors in the forebrain, has not been determined. Using a pharmacological approach, we investigated the role of NR2A and NR2B subtypes in the regulation of NMDA-induced dendritic translation of a GFP reporter mRNA controlled by CaMKII untranslated regions (UTRs). We found that ifenprodil and Ro25-6981, two specific inhibitors of NR2B-containing NMDA receptors, did not affect dendritic GFP synthesis induced by NMDA. In contrast, NVP-AAM077, an antagonist that preferentially blocks the NR2A subtype, completely abolished NMDA-induced GFP synthesis in dendrites. Our results together suggest that NR2A but not NR2B subtypes are indispensable for NMDA receptor-dependent dendritic protein synthesis.