Individual Differences in Epigenetic Regulation of Emotional Learning

项目总结/摘要 该提案旨在为通过NIDA夏季确定的本科生提供科学培训 研究实习计划。该研究项目的重点是确定共同的神经生物学底物 这可能使人容易上瘾，也容易患上经常同时发生的疾病，如创伤后精神障碍， 应激障碍（PTSD）。巴甫洛夫条件反射程序将用于区分“符号跟踪”大鼠， 倾向于将高水平的动机重要性归因于离散的预测线索，而在很大程度上忽略了 背景，从“目标跟踪”大鼠，使更多的使用背景，以适当地修改他们的情绪 应答信号跟踪大鼠更容易出现线索触发的成瘾和PTSD样行为，而不是目标， 追踪器这些行为特征的神经生物学基础将通过测试 已知介导动机性的关键边缘回路内的功能连接中的符号和目标追踪器 行为，即从腹侧海马到丘脑核的通路。神经元活动也将 操纵使用病毒载体测试的因果关系的影响条件动机反应， 食欲和厌恶的线索和背景。这些实验将检验目标追踪者 使用来自海马体输入的上下文信息来适当地修改 皮层下对与情绪突出事件相关的线索的反应。该项目将培养一个有前途的 科学家和帮助澄清潜在的神经生物学途径成瘾和经常共同发生的疾病， 这是一个重要的公共卫生优先事项。

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.