NF-κB transcription factor is required for inhibitory avoidance long-term memory in mice

Authors

  • Ramiro Freudenthal,

    1. 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, Pab. II, 2do piso (1428EHA), Buenos Aires, Argentina
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    • *

      R.F. and M.B. contributed equally to this study.

  • Mariano M. Boccia,

    1. Laboratorio de Neurofarmacología de Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 5to piso (C1113AAD) Buenos Aires, Argentina
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    • *

      R.F. and M.B. contributed equally to this study.

  • Gabriela B. Acosta,

    1. Instituto de Investigaciones Farmacológicas (ININFA-CONICET), Junín 956, 5to piso (C1113AAD), Buenos Aires, Argentina.
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  • Mariano G. Blake,

    1. Laboratorio de Neurofarmacología de Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 5to piso (C1113AAD) Buenos Aires, Argentina
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  • Emiliano Merlo,

    1. 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, Pab. II, 2do piso (1428EHA), Buenos Aires, Argentina
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  • Carlos M. Baratti,

    1. Laboratorio de Neurofarmacología de Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 5to piso (C1113AAD) Buenos Aires, Argentina
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  • Arturo Romano

    1. 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, Pab. II, 2do piso (1428EHA), Buenos Aires, Argentina
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Dr Arturo Romano, as above.
E-mail: aromano@fbmc.fcen.uba.ar

Abstract

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-κB (NF-κB) family of TFs in memory and neural plasticity. Here we found that two independent inhibitors of NF-κB 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-κB consensus sequence (κB decoy). Conversely, one base mutation of the κB decoy (mut-κB decoy) injection did not affect long-term memory. Accordingly, the κB decoy inhibited NF-κB in hippocampus 2 h after injection but no inhibition was found with mut-κB decoy administration. A temporal course of hippocampal NF-κB activity after training was determined. Unexpectedly, an inhibition of NF-κB was found 15 min after training in shocked and unshocked groups when compared with the naïve group. Hippocampal NF-κB 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-κB 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-κB activity being regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.

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