Spotlight on the July 19 Issue

Abstract Alcohol use is highly prevalent in the United States and across world, every year millions of people suffer from alcohol disorders (AUDs). While genetic contribution to developing AUDs estimated be 50-60%, many underlying molecular mechanisms remain unclear. Previous studies our lab revealed that Drosophila lacking RhoGAP18B Ras Suppressor 1 (Rsu1) display reduced sensitivity ethanol-induced sedation. Both Rsu1 are negative regulators small Rho-family GTPase, Rac1, a modulator actin dynamics. Here we investigate role Rac1 its downstream target, actin-severing protein cofilin, consumption preference. We show these two dynamics can alter experience-dependent preference bidirectional manner: expressing either activated or dominant-negative cofilin mushroom bodies (MB) abolishes Conversely, MB expression lead faster acquisition Our data activity key determining rate preference, revealing critical regulation development voluntary self-administration Drosophila. Significance Statement The risks for an disorder (AUD) strongly determined by factors. Understanding genes contribute risk therefore necessary first step targeted therapeutic intervention. cytoskeleton bidirectionally determine self-administration, highlighting this process as mechanism contributing AUD development.