The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories.
Previously formed memories are susceptible to disruption immediately after recall due to a necessity to be reconsolidated after retrieval. Protein translation mechanisms have been widely implicated as being necessary for memory reconsolidation, but gene transcription mechanisms have been much less extensively studied in this context. We found that retrieval of contextual conditioned fear memories activates the NF-kappaB pathway to regulate histone H3 phosphorylation and acetylation at specific gene promoters in hippocampus, specifically via IKKalpha and not the NF-kappaB DNA-binding complex. Behaviorally, we found that inhibition of IKKalpha regulation of either chromatin structure or NF-kappaB DNA-binding complex activity leads to impairments in fear memory reconsolidation, and that elevating histone acetylation rescues this memory deficit in the face of IKK blockade. These data provide insights into IKK-regulated transcriptional mechanisms in hippocampus that are necessary for memory reconsolidation.
Lubin
Farah D
FD
The Evelyn F. McKnight Brain Institute, Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Sweatt
J David
JD
D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D002843:Chromatin / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D006657:Histones / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors; D000097782:NF-kappaB-Inducing Kinase
D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D000097782:NF-kappaB-Inducing Kinase