The Role of Neuron-Specific Nucleosome Remodeling in Cocaine-Associated Memory and Synaptic Plasticity
- Author(s): White, Andre
- Advisor(s): Wood, Marcelo A
- et al.
Recent evidence have implicated epigenetic mechanisms in drug-associated memory formation. A possible role for one major epigenetic mechanism, nucleosome remodeling, in drug-associated memory formation has been largely unexplored. The present dissertation examined mice with genetic manipulations targeting a neuron-specific nucleosome remodeling complex subunit, BAF53b. These mice displayed deficits in cocaine-associated memory that were more severe in BAF53b dominant-negative transgenic mice compared to BAF53b heterozygous knockout mice. Similar to the memory deficits, theta-induced long-term potentiation (theta-LTP) in the nucleus accumbens (NAc) was significantly impaired in slices taken from BAF53b transgenic mutant mice but not heterozygous knockout mice. Further studies indicated that theta-LTP in the NAc is dependent on TrkB receptor activation, and that BDNF rescues theta-LTP and cocaine-associated memory in BAF53b transgenic mice. My studies suggest a role for BAF53b in NAc neuronal function required for cocaine-associated memories. Furthermore, targeting BDNF/TrkB activation in the nucleus accumbens may overcome memory and plasticity deficits linked to BAF53b mutations.