HDAC activity is required for BDNF to increase quantal neurotransmitter release and dendritic spine density in CA1 pyramidal neurons

Gaston Calfa, Christopher A. Chapleau, Susan Campbell, Takafumi Inoue, Sarah J. Morse, Farah D. Lubin, Lucas Pozzo-Miller

Research output: Contribution to journalArticle

40 Citations (Scopus)


Molecular mechanisms involved in the strengthening and formation of synapses include the activation and repression of specific genes or subsets of genes by epigenetic modifications that do not alter the genetic code itself. Chromatin modifications mediated by histone acetylation have been shown to be critical for synaptic plasticity at hippocampal excitatory synapses and hippocampal-dependent memory formation. Considering that brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity and behavioral adaptations, it is not surprising that regulation of this gene is subject to histone acetylation changes during synaptic plasticity and hippocampal-dependent memory formation. Whether the effects of BDNF on dendritic spines and quantal transmitter release require histone modifications remains less known. By using two different inhibitors of histone deacetylases (HDACs), we describe here that their activity is required for BDNF to increase dendritic spine density and excitatory quantal transmitter release onto CA1 pyramidal neurons in hippocampal slice cultures. These results suggest that histone acetylation/deacetylation is a critical step in the modulation of hippocampal synapses by BDNF. Thus, mechanisms ofepigenetic modulation of synapse formation and function are novel targets to consider for the amelioration of symptoms of intellectual disabilities and neurodegenerative disorders associated with cognitive and memory deficits.

Original languageEnglish
Pages (from-to)1493-1500
Number of pages8
Issue number7
Publication statusPublished - 2012 Jul 1



  • BDNF
  • Dendritic spines
  • Epigenetics
  • Hippocampal slice cultures
  • Histone deacetylase
  • Quantal release
  • SAHA
  • TSA

ASJC Scopus subject areas

  • Cognitive Neuroscience

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