Consolidation of synaptic plasticity appears to require transcription, but how the nucleus is informed in this context remains unknown. Because NMDA receptor antagonists have been shown to interfere with action potential generation, the issue of whether or not a synaptically-generated signal is required for nuclear signaling is currently unresolved. Here we show that pharmacologic maintenance of action potentials during NMDA receptor blockade allows for NMDA receptor-independent transcription factor binding and arc gene expression, both of which were previously thought to be NMDA receptor dependent. These data suggest that types of signaling in the nucleus previously attributed to NMDA-receptor dependent synapse-to-nucleus signals can be initiated in the absence of NMDA-receptor dependent synaptic plasticity.