Abstracts - Speakers

First Annual Waggoner Center Advance - March 22, 2013

Alfredo Ghezzi, PhD

Research Associate, Atkinson Lab

Epigenetic Modulation of a Pre-synaptic Gene Network Orchestrates the Development of Tolerance to Alcohol in Drosophila

Sustained or repeated exposure to sedating drugs such as alcohol and anesthetics triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. Adaptation to addictive drugs appear to involve long-term changes in the transcriptional activity of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions to signal and maintain the altered transcriptional state. For instance, alcohol-induced changes in histone acetylation have been shown to trigger changes in neurons that lead to the alcoholism endophenotypes of tolerance and dependence. These changes are believed to be of central importance in producing the addictive state. Here, we use Drosophila to explore the mechanisms behind the epigenetic modifications underlying alcohol tolerance. Through a combination of genome-wide surveys of alcohol-induced histone modifications and behavioral analysis of mutant and RNAi lines, we have identified a network of genes with roles in the modulation of neural activity that are essential for the development of alcohol tolerance. Furthermore, we find that the Drosophila histone-acetyl transferase CBP, contributes to the epigenetic regulation during the development of tolerance to alcohol. Through this approach, we have begun to decipher the overarching transcriptional events orchestrating the adaptations that contribute to alcohol addiction.