Individual Differences in Epigenetic Regulation of Emotional Learning

项目总结/文摘

PROJECT SUMMARY/ABSTRACT This proposal is intended to offer scientific training to an undergraduate identified through the NIDA Summer Research Internship Program. The research project focuses on identifying common neurobiological substrates that may confer vulnerability both to addiction and to frequently co-occurring disorders such as post-traumatic stress disorder (PTSD). Pavlovian conditioning procedures will be used to distinguish “sign-tracking” rats that tend to attribute high levels of motivational significance to discrete predictive cues while largely ignoring context, from “goal-tracking” rats that make more use of context to appropriately modify their emotional responses. Sign-tracking rats are more prone to cue-triggered addiction- and PTSD-like behaviors than goal- trackers. The neurobiological basis of these behavioral traits will be explored by testing for differences between sign- and goal-trackers in functional connectivity within key limbic circuits known to mediate motivated behavior, namely pathways from ventral hippocampus to nucleus accumbens. Neuronal activity will also be manipulated using viral vectors to test for a causal influence on conditioned motivational responses to appetitive and aversive cues and contexts. These experiments will test the hypothesis that goal-trackers have an increased capacity to use contextual information derived from hippocampal inputs to appropriately modify subcortical responses to cues associated with emotionally salient events. The project will train a promising scientist and help clarify potential neurobiological pathways to addiction and frequently co-occurring disorders, which is a significant public health priority.