Role of Action Potentials in Regulating Gene Transcription: Relevance to LTP
The late phase of Long Term Potentiation (LTP) appears to require transcription, but how the nucleus is informed remains unknown. We propose that calcium elevation from multiple action potentials serves as the signal rather than an NMDA receptor-dependent signal transported from synapses. We find that NMDA receptor antagonists interfere with action potential generation and thus do not resolve the issue. Pharmacologic restoration of action potentials in the presence of NMDA receptor antagonists shows that ERK activation, transcription factor binding, and arc gene expression, previously all shown or thought to be NMDA receptor dependent, are maintained. These data demonstrate that types of signaling in the nucleus, previously attributed to NMDA-receptor dependent synapse-to-nucleus signals, can be initiated by action potentials. Action potential-mediated calcium increases can provide a fast and effective signal in the nucleus that may be an important factor in LTP consolidation.
KeywordsNMDA Receptor Long Term Potentiation Action Potential Generation Regulate Gene Transcription NMDAR Antagonist
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