Selective targeting of newly synthesized Arc mRNA to active synapses requires NMDA receptor activation

Newly synthesized Are mRNA is selectively targeted to synapses that have ex perienced particular patterns of activity. Here, we demonstrate that the ta rgeting requires NMDA receptor activation. Are expression was induced by an electroconvulsive seizure, and the newly synthesized mRNA was then targete d to synaptic sites by activating the perforant path projections to the den tate gyrus. When micropipette electrodes containing NMDA receptor antagonis ts (MK801 or APV) were positioned in the dentate gyrus during the stimulati on period, newly synthesized Are mRNA was transported into dendrites but di d not localize in the activated lamina; instead, the mRNA remained diffusel y distributed. AMPA receptor antagonists (CNQX) blocked targeting of Are mR NA in a small region, and mGluR antagonists (MCPG) did not affect localizat ion. These results demonstrate that NMDA receptor activation is required fo r the targeting of Are mRNA to active synapses.