Neural Mechanisms Underlying Maladaptive Reward Memories in Drosophila

INVESTIGATOR: Kristin Scaplan, Bryant University
MENTOR: Karla Kaun, Brown University


ABSTRACT: Alcohol addiction constitutes one of the most serious public health problems worldwide. Despite its devastating impact, there are few effective treatments. Circuit based approaches to treat addiction provide a powerful opportunity to develop more specific and effective treatments. However, circuit complexity has made it difficult to achieve a comprehensive understanding of the mechanisms underlying enduring preferences for alcohol associated cues. I will capitalize on the genetic tractability of Drosophila to interrogate precisely how identified memory circuits are altered by alcohol to drive maladaptive behaviors. Specifically, I will use a combination of optogenetics, thermogenetics, and in vivo calcium imaging to: 1) capture the precise changes in dopamine neural dynamics while flies learn to associate odor cues with alcohol intoxication, 2) determine whether similar artificial activation patterns of dopamine neurons is sufficient to induce maladaptive memories for natural rewards, and 3) understand how alcohol memories are stabilized in recently identified regions downstream of alcohol memory circuits. I expect that dopamine dynamics will significantly increase across alcohol exposures and this increase is sufficient to drive maladaptive reward seeking behavior. Further, I expect that downstream convergent regions play a critical role in behavioral flexibility and disruption to these functional connections results in memories that lack flexibility and drive maladaptive reward seeking. Ultimately, understanding general circuitry principles described first in Drosophila will provide insight to how alcohol co-opts more complex circuits to create enduring preference for alcohol and drive maladaptive choice.

HUMAN HEALTH RELEVANCE:  Alcohol Use Disorder (AUD) is a debilitating disorder, which manifests as problematic patterns of alcohol use and cravings in the face of abstinence. Here we use the fruit fly to understand how alcohol co-opts neural circuits to drive maladaptive drug seeking behaviors. Understanding how these circuits change in the context of alcohol is critical for the development of more specific and effective circuit-based AUD treatment strategies.