NF-kappaB transcription factor is required for inhibitory avoidance long-term memory in mice.
Although it is generally accepted that memory consolidation requires regulation of gene expression, only a few transcription factors (TFs) have been clearly demonstrated to be specifically involved in this process. Increasing research data point to the participation of the Rel/nuclear factor-kappaB (NF-kappaB) family of TFs in memory and neural plasticity. Here we found that two independent inhibitors of NF-kappaB induced memory impairment in the one-trial step-through inhibitory avoidance paradigm in mice: post-training administration of the drug sulfasalazine and 2 h pretraining administration of a double-stranded DNA oligonucleotide containing the NF-kappaB consensus sequence (kappaB decoy). Conversely, one base mutation of the kappaB decoy (mut-kappaB decoy) injection did not affect long-term memory. Accordingly, the kappaB decoy inhibited NF-kappaB in hippocampus 2 h after injection but no inhibition was found with mut-kappaB decoy administration. A temporal course of hippocampal NF-kappaB activity after training was determined. Unexpectedly, an inhibition of NF-kappaB was found 15 min after training in shocked and unshocked groups when compared with the naïve group. Hippocampal NF-kappaB was activated 45 min after training in both shocked and unshocked groups, decreasing 1 h after training and returning to basal levels 2 and 4 h after training. On the basis of the latter results, we propose that activation of NF-kappaB in hippocampus is part of the molecular mechanism involved in the storage of contextual features that constitute the conditioned stimulus representation. The results presented here provide the first evidence to support NF-kappaB activity being regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.
Freudenthal
Ramiro
R
Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IFIByNE, CONICET, Ciudad Universitaria, Buenos Aires, Argentina.
Boccia
Mariano M
MM
Acosta
Gabriela B
GB
Blake
Mariano G
MG
Merlo
Emiliano
E
Baratti
Carlos M
CM
Romano
Arturo
A
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D004597:Electroshock; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D012460:Sulfasalazine / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
D016328:NF-kappa B; D014157:Transcription Factors; D012460:Sulfasalazine; D007213:Indomethacin