Year: 2019
Type: dissertation
Abstract: Epigenetic modifications are key regulators of neural plasticity and are implicated in various forms of experience-induced changes in behavior, including memory and addiction. Histone variants are newly identified epigenetic regulators of neural plasticity and the histone variant H2A.Z has been shown to regulate memory formation, suggesting a potential role in other types of plasticity. The goal of this thesis was to determine whether H2A.Z regulates the development of preference (index of reward) and sensitization to nicotine by isolating the unique contributions of two H2A.Z-encoding genes, H2afv and H2Afz. Using conditional-inducible knockout mice for each gene, we showed that H2Afv deletion eliminated conditioned place preference (CPP) and locomotor sensitization to nicotine, whereas H2Afz deletion selectively impaired locomotor sensitization. This is the first study to demonstrate a gene-specific effect of H2A.Z on behavior and to implicate H2A.Z in regulating responses to psychostimulants, suggesting that H2A.Z may contribute to risk for nicotine addiction.
Source: TSpace (University of Toronto)
Author: Carl Frank David Steininger
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3033668237