Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation

Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance both memory and synaptic plasticity. The current model for the action of HDAC inhibitors assumes that they alter gene expression globally and thus affect memory processes in a nonspecific manner. Here, we show that the enhancement of hippocampus-dependent memory and hippocampal synaptic plasticity by HDAC inhibitors is mediated by the transcription factor cAMP response element-binding protein (CREB) and the recruitment of the transcriptional coactivator and histone acetyltransferase CREB-binding protein (CBP) via the CREB-binding domain of CBP. Furthermore, we show that the HDAC inhibitor trichostatin A does not globally alter gene…

• DA
  David and Lucile Packard Foundation
• WF
  Whitehall Foundation
• UO
  University of Pennsylvania
• NI
  National Institutes of Health

  Award: HL07953