BDNF rescues BAF53b-dependent synaptic plasticity and cocaine-associated memory in the nucleus accumbens

André O. White, Enikö A. Kramár, Alberto J. López, Janine L. Kwapis, John Doan, David Saldana, M. Felicia Davatolhagh, Yasaman Alaghband, Mathew Blurton-Jones, Dina P. Matheos, Marcelo A. Wood

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Abstract

Recent evidence implicates epigenetic mechanisms in drug-associated memory processes. However, a possible role for one major epigenetic mechanism, nucleosome remodelling, in drug-associated memories remains largely unexplored. Here we examine mice with genetic manipulations targeting a neuron-specific nucleosome remodelling complex subunit, BAF53b. These mice display deficits in cocaine-associated memory that are more severe in BAF53b transgenic mice compared with BAF53b heterozygous mice. Similar to the memory deficits, theta-induced long-term potentiation (theta-LTP) in the nucleus accumbens (NAc) is significantly impaired in slices taken from BAF53b transgenic mice but not heterozygous mice. Further experiments indicate that theta-LTP in the NAc is dependent on TrkB receptor activation, and that BDNF rescues theta-LTP and cocaine-associated memory deficits in BAF53b transgenic mice. Together, these results suggest a role for BAF53b in NAc neuronal function required for cocaine-associated memories, and also that BDNF/TrkB activation in the NAc may overcome memory and plasticity deficits linked to BAF53b mutations.

Original languageEnglish (US)
Article number11725
JournalNature communications
Volume7
DOIs
StatePublished - May 26 2016

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    White, A. O., Kramár, E. A., López, A. J., Kwapis, J. L., Doan, J., Saldana, D., Davatolhagh, M. F., Alaghband, Y., Blurton-Jones, M., Matheos, D. P., & Wood, M. A. (2016). BDNF rescues BAF53b-dependent synaptic plasticity and cocaine-associated memory in the nucleus accumbens. Nature communications, 7, [11725]. https://doi.org/10.1038/ncomms11725