Acetylation of nuclear factor-kappaB in rat amygdala improves long-term but not short-term retention of fear memory.
Memory consolidation is mediated by new protein synthesis. However, the transcriptional pathways induced in neurons by behavioral training that activate gene responses have yet to be fully delineated. We have previously shown that nuclear factor kappaB (NF-kappaB) is activated in the amygdala after fear conditioning. Here we report that fear conditioning resulted in an increase in histone acetyl-transferase activity, the association between NF-kappaB p65 and CBP, and the increase in acetylated p65. Pretreating animals with histone deacetylase (HDAC) inhibitors prolonged the nuclear expression of acetyl-p65 and increased its DNA binding activity. Consistent with these results, HDAC inhibitors enhanced long-term but not short-term fear memory, and this effect was attenuated by kappaB decoy DNA, whereas scrambled DNA was without effect. This study provides evidence that HDAC-mediated deacetylation functions as an intranuclear molecular switch culminating in the termination of NF-kappaB transcriptional response that is involved in the formation of fear memory.
Yeh
Shiu-Hwa
SH
Institute of Basic Medical Sciences, Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan.
Lin
Chia-Ho
CH
Gean
Po-Wu
PW
D000107:Acetylation; D000679:Amygdala / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002135:Calcium-Binding Proteins; D005239:Fear / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors; D017774:Long-Term Potentiation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000502:physiology; D012153:Retention, Psychology / Q000502:physiology*; D050863:Synaptotagmin I; D050857:Synaptotagmins; D013995:Time
D002135:Calcium-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; D050857:Synaptotagmins