Our hosting provider will be performing UPS maintenance on Tuesday, Oct 25, 2016 between 8 AM and 5 PM PDT. SciCrunch searching services will be down during this time.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

HDAC2 negatively regulates memory formation and synaptic plasticity.


Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment.

Pubmed ID: 19424149


  • Guan JS
  • Haggarty SJ
  • Giacometti E
  • Dannenberg JH
  • Joseph N
  • Gao J
  • Nieland TJ
  • Zhou Y
  • Wang X
  • Mazitschek R
  • Bradner JE
  • DePinho RA
  • Jaenisch R
  • Tsai LH



Publication Data

May 7, 2009

Associated Grants

  • Agency: NIDA NIH HHS, Id: R01 DA028301
  • Agency: NIDA NIH HHS, Id: R01 DA028301-02
  • Agency: NINDS NIH HHS, Id: R01 NS051874
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Butyrates
  • Dendritic Spines
  • Electrical Synapses
  • Female
  • Gene Expression Regulation
  • Hippocampus
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
  • Hydroxamic Acids
  • Learning
  • Male
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons
  • Promoter Regions, Genetic
  • Repressor Proteins
  • Sodium