NF-kappaB transcription factor is required for inhibitory avoidance long-term memory in mice. European Journal of Neuroscience

RAMIRO FREUDENTHAL,; MARIANO BOCCIA,; GABRIELA ACOSTA,; MARIANO BLAKE,; EMILIANO MERLO,; CARLOS BARATTI,; ARTURO GABRIEL ROMANO

EUROPEAN JOURNAL OF NEUROSCIENCE

Año: 2005 vol. 21 p. 2845 - 2852

0953-816X

Although it is generally accepted that memory consolidation requires regulation of gene expression, only few transcription factors (TFs) were clearly demonstrated to be specifically involved in this process. Increasing research data point to the participation of Rel/NF-kB family of TFs in memory and neural plasticity. Here we found that two independent inhibitors of NF-kB induced memory impairment in the one-trial step-through inhibitory avoidance paradigm in mice: post-training administration of the drug sulfasalazine and 2 h pre-training administration of a double stranded DNA oligonucleotide containing the NF-kB consensus sequence (kB decoy). Conversely, one base mutation of kB decoy (mut-kB decoy) injection did not affect long-term memory. Accordingly, kB decoy inhibited NF-kB in hippocampus two h after injection but no inhibition was found with mut-kB decoy administration. A temporal course of hippocampal NF-kB activity after training was determined. Unexpectedly, an inhibition of NF-kB was found 15 min after training in shocked and unshocked groups when compared with naïve group. Hippocampal NF-kB 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-kB 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 supporting that NF-kB activity is regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.