 |
The Journal of Neuroscience, June 6, 2007, 27(23):6128-6140; doi:10.1523/JNEUROSCI.0296-07.2007
Previous Article | Next Article 
Behavioral/Systems/Cognitive
Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation
Christopher G. Vecsey,1
Joshua D. Hawk,1
K. Matthew Lattal,4
Joel M. Stein,3
Sara A. Fabian,2
Michelle A. Attner,2
Sara M. Cabrera,5
Conor B. McDonough,1
Paul K. Brindle,6
Ted Abel,1,2,3 and
Marcelo A. Wood5
1Neuroscience Graduate Group, 2Department of Biology, and 3Cell and Molecular Biology Graduate Group, University of Pennsylvania 19104, 4Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97239, 5Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, California 92697, and 6Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Correspondence should be addressed to either of the following: Marcelo A. Wood, Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-3800, Email: mwood{at}uci.edu; or Ted Abel, Department of Biology, University of Pennsylvania, 204G Carolyn Lynch Laboratory, Philadelphia, PA 19104, Email: abele{at}sas.upenn.edu
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.
Key words: histone deacetylase inhibitors; hippocampus-dependent memory; CREB-binding protein; KIX domain; Nr4a1; Nr4a2
Received Oct. 25, 2005;
revised April 26, 2007;
accepted April 26, 2007.
Correspondence should be addressed to either of the following: Marcelo A. Wood, Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-3800, Email: mwood{at}uci.edu; or Ted Abel, Department of Biology, University of Pennsylvania, 204G Carolyn Lynch Laboratory, Philadelphia, PA 19104, Email: abele{at}sas.upenn.edu
This article has been cited by other articles:

|
 |

|
 |
 
K. Koshibu, J. Graff, M. Beullens, F. D. Heitz, D. Berchtold, H. Russig, M. Farinelli, M. Bollen, and I. M. Mansuy
Protein Phosphatase 1 Regulates the Histone Code for Long-Term Memory
J. Neurosci.,
October 14, 2009;
29(41):
13079 - 13089.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Federman, M. S. Fustinana, and A. Romano
Histone acetylation is recruited in consolidation as a molecular feature of stronger memories
Learn. Mem.,
September 30, 2009;
16(10):
600 - 606.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Langley, C. Brochier, and M. A. Rivieccio
Targeting Histone Deacetylases as a Multifaceted Approach to Treat the Diverse Outcomes of Stroke
Stroke,
August 1, 2009;
40(8):
2899 - 2905.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Stafford and K. M. Lattal
Direct comparisons of the size and persistence of anisomycin-induced consolidation and reconsolidation deficits
Learn. Mem.,
July 24, 2009;
16(8):
494 - 503.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. W. Akhtar, J. Raingo, E. D. Nelson, R. L. Montgomery, E. N. Olson, E. T. Kavalali, and L. M. Monteggia
Histone Deacetylases 1 and 2 Form a Developmental Switch That Controls Excitatory Synapse Maturation and Function
J. Neurosci.,
June 24, 2009;
29(25):
8288 - 8297.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. P. Stefanko, R. M. Barrett, A. R. Ly, G. K. Reolon, and M. A. Wood
Modulation of long-term memory for object recognition via HDAC inhibition
PNAS,
June 9, 2009;
106(23):
9447 - 9452.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Saavedra-Rodriguez, A. Vazquez, H. G. Ortiz-Zuazaga, N. E. Chorna, F. A. Gonzalez, L. Andres, K. Rodriguez, F. Ramirez, A. Rodriguez, and S. P. de Ortiz
Identification of Flap Structure-Specific Endonuclease 1 as a Factor Involved in Long-Term Memory Formation of Aversive Learning
J. Neurosci.,
May 6, 2009;
29(18):
5726 - 5737.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Adachi, A. E. Autry, H. E. Covington III, and L. M. Monteggia
MeCP2-Mediated Transcription Repression in the Basolateral Amygdala May Underlie Heightened Anxiety in a Mouse Model of Rett Syndrome
J. Neurosci.,
April 1, 2009;
29(13):
4218 - 4227.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. M. Alberini
Transcription Factors in Long-Term Memory and Synaptic Plasticity
Physiol Rev,
January 1, 2009;
89(1):
121 - 145.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Jiang, B. Langley, F. D. Lubin, W. Renthal, M. A. Wood, D. H. Yasui, A. Kumar, E. J. Nestler, S. Akbarian, and A. C. Beckel-Mitchener
Epigenetics in the Nervous System
J. Neurosci.,
November 12, 2008;
28(46):
11753 - 11759.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. M. Barrett and M. A. Wood
Beyond transcription factors: The role of chromatin modifying enzymes in regulating transcription required for memory
Learn. Mem.,
June 26, 2008;
15(7):
460 - 467.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. N. Saha and S. M. Dudek
Action Potentials: To the Nucleus and Beyond
Experimental Biology and Medicine,
April 1, 2008;
233(4):
385 - 393.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Leng, M.-H. Liang, M. Ren, Z. Marinova, P. Leeds, and D.-M. Chuang
Synergistic Neuroprotective Effects of Lithium and Valproic Acid or Other Histone Deacetylase Inhibitors in Neurons: Roles of Glycogen Synthase Kinase-3 Inhibition
J. Neurosci.,
March 5, 2008;
28(10):
2576 - 2588.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. W. Bredy and M. Barad
The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear
Learn. Mem.,
January 3, 2008;
15(1):
39 - 45.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. B. Chwang, J. S. Arthur, A. Schumacher, and J. D. Sweatt
The Nuclear Kinase Mitogen- and Stress-Activated Protein Kinase 1 Regulates Hippocampal Chromatin Remodeling in Memory Formation
J. Neurosci.,
November 14, 2007;
27(46):
12732 - 12742.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|

|