Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB: CBP-dependent transcriptional activation

Christopher G. Vecsey, Joshua D. Hawk, Kennon (Matt) Lattal, Joel M. Stein, Sara A. Fabian, Michelle A. Attner, Sara M. Cabrera, Conor B. McDonough, Paul K. Brindle, Ted Abel, Marcelo A. Wood

Research output: Contribution to journalArticle

547 Citations (Scopus)

Abstract

Histone deacetylase(HDAC)inhibitors increase histone acetylation and enhance bothmemoryand 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 theHDACinhibitor trichostatinAdoes 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.

Original languageEnglish (US)
Pages (from-to)6128-6140
Number of pages13
JournalJournal of Neuroscience
Volume27
Issue number23
DOIs
StatePublished - Jun 6 2007

Fingerprint

CREB-Binding Protein
Cyclic AMP Response Element-Binding Protein
Neuronal Plasticity
Histone Deacetylase Inhibitors
Protein Binding
Transcriptional Activation
Gene Expression
Histone Acetyltransferases
Acetylation
Histones
Hippocampus
Carrier Proteins
Transcription Factors

Keywords

  • CREB-binding protein
  • Hippocampus-dependent memory
  • Histone deacetylase inhibitors
  • KIX domain
  • Nr4a1
  • Nr4a2

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB : CBP-dependent transcriptional activation. / Vecsey, Christopher G.; Hawk, Joshua D.; Lattal, Kennon (Matt); Stein, Joel M.; Fabian, Sara A.; Attner, Michelle A.; Cabrera, Sara M.; McDonough, Conor B.; Brindle, Paul K.; Abel, Ted; Wood, Marcelo A.

In: Journal of Neuroscience, Vol. 27, No. 23, 06.06.2007, p. 6128-6140.

Research output: Contribution to journalArticle

Vecsey, CG, Hawk, JD, Lattal, KM, Stein, JM, Fabian, SA, Attner, MA, Cabrera, SM, McDonough, CB, Brindle, PK, Abel, T & Wood, MA 2007, 'Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB: CBP-dependent transcriptional activation', Journal of Neuroscience, vol. 27, no. 23, pp. 6128-6140. https://doi.org/10.1523/JNEUROSCI.0296-07.2007
Vecsey, Christopher G. ; Hawk, Joshua D. ; Lattal, Kennon (Matt) ; Stein, Joel M. ; Fabian, Sara A. ; Attner, Michelle A. ; Cabrera, Sara M. ; McDonough, Conor B. ; Brindle, Paul K. ; Abel, Ted ; Wood, Marcelo A. / Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB : CBP-dependent transcriptional activation. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 23. pp. 6128-6140.
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