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

Nat Commun. 2016 May 26;7:11725. doi: 10.1038/ncomms11725.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Line
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cocaine
  • Cocaine-Related Disorders / metabolism*
  • Cocaine-Related Disorders / physiopathology
  • Female
  • Long-Term Potentiation / physiology
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / metabolism*
  • Memory Disorders / physiopathology
  • Mice, Knockout
  • Mice, Transgenic
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / physiopathology
  • Receptor, trkB / metabolism

Substances

  • Actl6b protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Chromosomal Proteins, Non-Histone
  • Receptor, trkB
  • Cocaine