Individual Differences in Epigenetic Regulation of Emotional Learning

项目摘要/摘要 这项提议旨在为通过NIDA夏季认证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常见的神经生物学底物。 这可能会使人既容易上瘾，又容易患上经常同时发生的疾病，如创伤后疾病 应激障碍(PTSD)。巴甫洛夫条件反射程序将被用来区分那些 倾向于将高水平的激励意义归因于离散的预测性线索，而在很大程度上忽略了 情境，从更多地利用情境来适当调整自己的情绪的“目标跟踪”老鼠 回应。手势跟踪的大鼠比目标大鼠更容易出现线索触发的成瘾和创伤后应激障碍样行为 追踪者。这些行为特征的神经生物学基础将通过测试 在关键边缘回路内的功能连接中的手势和目标追踪器，已知调解动机 行为，即从腹侧海马区到伏隔核的通路。神经元的活动也会 使用病毒载体来测试对条件性动机反应的因果影响 有胃口和厌恶的线索和背景。这些实验将检验这样一个假设，即目标追踪者 使用来自海马体输入的上下文信息来适当修改 皮层下对情绪显著事件相关线索的反应。该项目将培养一位有前途的 科学家并帮助阐明成瘾和常见共生疾病的潜在神经生物学途径， 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.