Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity Via CREB:CBP-dependent Transcriptional Activation

Overview

Journal J Neurosci

Specialty Neurology

Date 2007 Jun 8

PMID 17553985

Citations 405

Authors

Christopher G Vecsey

Joshua D Hawk

K Matthew Lattal

Joel M Stein

Sara A Fabian

Michelle A Attner

Sara M Cabrera

Conor B McDonough

Paul K Brindle

Ted Abel

Marcelo A Wood

Affiliations

Soon will be listed here.

Abstract

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 expression but instead increases the expression of specific genes during memory consolidation. Our results suggest that HDAC inhibitors enhance memory processes by the activation of key genes regulated by the CREB:CBP transcriptional complex.

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