Skip to main content
Open Access Publications from the University of California

UC Irvine

UC Irvine Electronic Theses and Dissertations bannerUC Irvine

The Role of Neuron-Specific Nucleosome Remodeling in Cocaine-Associated Memory and Synaptic Plasticity

Creative Commons 'BY-NC-ND' version 4.0 license

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.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View