NUCLEAR FACTOR KAPPAB-DEPENDENT HISTONE ACETYLATION OF CAMK2D GENE IS SPECIFICALLY INVOLVED IN MEMORY PERSISTENCE.

FEDERMAN N; DE LA FUENTE V; ZALCMAN G; ROMANO A

Huerta Grande, Córdoba

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2013

Sociedad Argentina de Investigación en Neurociencias

We have demonstrated that histone acetylation is a specific molecular signature of enduring memories consolidation. To gain insight into the specific gene expression effect of the induction of this epigenetic mechanism, we studied the role in this mechanism of Nuclear factor κB (NF-κB) transcription factor during novel object recognition (NOR) memory persistence. To address this aim, we used three different training protocols: one group of mice received a weak training which did not induce long-term memory (LTM); other group which received a standard training which lead to 24hs LTM, and the last group received a strong training which induced 7 weeks LTM. We found that only after strong training, NF-κB inhibition impaired memory persistence and prevented the induction of general H3 acetylation. To determine the histone acetylation level in specific genome locations, we studied the promoter regions of two particular genes which were associated with neural plasticity and memory: Zif268 and CaMKII. We found an important increase in H3 acetylation at a specific NF-κB-regulated promoter region of the Camk2d gene, which was reversed by NF-κB inhibition. This H3 acetylation increment led to δCaMKII mRNA induction 6h after strong training, but not after weaker training protocols. This result showed that δCaMKII expression was only induced during consolidation of enduring memory. Our work presents a molecular link between transcription factor activation, epigenetic mechanism, and late gene expression in the regulation of memory persistence.