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HDAC activity is required for BDNF to increase quantal neurotransmitter release and dendritic spine density in CA1 pyramidal neurons
Author(s) -
Calfa Gaston,
Chapleau Christopher A.,
Campbell Susan,
Inoue Takafumi,
Morse Sarah J.,
Lubin Farah D.,
PozzoMiller Lucas
Publication year - 2012
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20990
Subject(s) - neuroscience , dendritic spine , synaptic plasticity , hippocampal formation , excitatory postsynaptic potential , metaplasticity , neurotrophic factors , histone , chemistry , synapse , epigenetics , biology , inhibitory postsynaptic potential , gene , biochemistry , receptor
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. © 2011 Wiley Periodicals, Inc.