NMDA receptor-independent control of transcription factors and gene expression.
Consolidation of synaptic plasticity seems to require transcription, but how the nucleus is informed in this context remains unknown. As 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 pharmacological 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.
Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, NC 27709, USA.
J Paige
JP
Adams
Rachel A
RA
Robinson
Eric D
ED
Hudgins
Erin M
EM
Wissink
Serena M
SM
Dudek
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009687:Nuclear Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline