Object recognition memory persistence involves histone acetylation in hippocampus

NOEL FEDERMAN; DE LA FUENTE, VERÓNICA; MARIA SOL FUSTIÑANA; ARTURO ROMANO

Washington

Congreso; SfN Meeting 2011; 2011

Society for Neuroscience

Long-term memory consolidation requires gene transcription. Transcriptional activation is controlled by transcription factors that interact with basal transcription machinery, remodeling chromatin structure by chemical modifications of histones. Acetylation is the most studied histone modification related to gene expression regulation. This process is regulated by histone acetylases (HATs) and deacetylases (HDACs). Here we found first that HDACS inhibitors administration in the hippocampus produced enhanced long-term recognition memory. Then, we found that standard and strong training produced object discrimination but not the weak training when tested a day later. However, 1 week later strong training showed significant higher levels of discrimination than standard training, indicating that produced a more persistent memory. Accordingly, only a strong training induced a general increase of H3 acetylation level in hippocampus 1 h after training. By contrast, neither a weak nor an intermediate training produced such increment. In order to evaluate the level of H3 acetylation in a particular gene, we performed ChIP assay for a promoter region of the zif268 gene. Accordingly with the increment of general H3 acetylation, we found in hippocampus, 1 h after training, a tenfold increment in H3 acetylation in that promoter only for strong training. Contrarily, weak and strong training did not produce significant increment with respect to controls. Based on our results, we propose that histone acetylation is a key mechanism in LTM persistence, functioning as a molecular signature of stronger memories.