An essential role for histone deacetylase 4 in synaptic plasticity and memory formation

Mi Sung Kim, M. Waseem Akhtar, Megumi Adachi, Melissa Mahgoub, Rhonda S Bassel-Duby, Ege T Kavalali, Eric N Olson, Lisa M Monteggia

Research output: Contribution to journalArticlepeer-review

194 Scopus citations


Histone deacetylases (HDACs), a family of enzymes involved in epigenetic regulation, have been implicated in the control of synaptic plasticity, as well as learning and memory. Previous work has demonstrated administration of pharmacological HDAC inhibitors, primarily those targeted to class I HDACs, enhance learning and memory as well as long-term potentiation. However, a detailed understanding of the role of class II HDACs in these processes remains elusive. Here, we show that selective loss of Hdac4 in brain results in impairments in hippocampal-dependent learning and memory and long-term synaptic plasticity. In contrast, loss of Hdac5 does not impact learning and memory demonstrating unique roles in brain for individual class II HDACs. These findings suggest that HDAC4 is a crucial positive regulator of learning and memory, both behaviorally and at the cellular level, and that inhibition of Hdac4 activity may have unexpected detrimental effects to these processes.

Original languageEnglish (US)
Pages (from-to)10879-10886
Number of pages8
JournalJournal of Neuroscience
Issue number32
StatePublished - Aug 8 2012

ASJC Scopus subject areas

  • Neuroscience(all)


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