The degree of histone acetylation/deacetylation is finely orchestrated by dynamic balance of antagonistic enzymes that “write” (HATs) and “erase” [histone deacetylases (HDACs)] acetylation sites (113, 118–121). Systemic administration of HDAC inhibitors (HDACi), such as sodium butyrate (NaB) or trichostatin A (TSA), can improve memory formation and also prevent or reverse cognitive impairments associated with normal and pathological aging. However, this enhancing effect of HDACi on HPC-dependent memory required accurate CREB activity (116, 117, 122). Furthermore, infusing HDACi directly to the HPC was not only effective in promoting HPC-dependent learning and memory processes but can also influence relative use of multiple memory processes by affecting transcriptional events within subcortical and PFC cortical structures (116, 123).
