Histone deacetylase inhibition via RGFP966 releases the brakes on sensory cortical plasticity and the specificity of memory formation

Kasia M. Bieszczad, Kiro Bechay, James R. Rusche, Vincent Jacques, Shashi Kudugunti, Wenyan Miao, Norman M. Weinberger, James L. McGaugh, Marcelo A. Wood

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories.

Original languageEnglish (US)
Pages (from-to)13124-13132
Number of pages9
JournalJournal of Neuroscience
Issue number38
StatePublished - Sep 23 2015

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)


  • Auditory cortex
  • Chromatin modification
  • Cortical plasticity
  • Epigenetics
  • Histone acetylation
  • Memory


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