Individual Differences in Epigenetic Regulation of Emotional Learning

情绪学习表观遗传调节的个体差异

• 批准号: 10399807
• 负责人: Jonathan David Morrow
• 金额: $ 1.45万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-31 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10399807
• 关键词: Address; Animal Model; Behavior; Behavioral; Complex; Cues; Desire for food; Diagnostic; Disease; Electrophysiology (science); Emotional; Event; Goals; Hippocampus (Brain); Individual Differences; Internships; Learning; Mediating; Mental disorders; Molecular; Motivation; National Institute of Drug Abuse; Neurobiology; Neurons; Nucleus Accumbens; Pathway interactions; Patients; Post-Traumatic Stress Disorders; Prevention strategy; Procedures; Rattus; Research; Research Personnel; Research Project Grants; Scientist; Techniques; Testing; Training; Viral Vector; addiction; classical conditioning; comorbidity; design; dual diagnosis; effective therapy; emotion regulation; epigenetic regulation; experimental study; motivated behavior; neuromechanism; programs; public health priorities; response; summer research; tool; trait; undergraduate student

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.

项目摘要/摘要 该建议旨在为在NIDA夏季确定的本科生提供科学培训 研究实习计划。该研究项目着重于识别常见的神经生物学基材 这可能会导致成瘾和经常出现的疾病（例如创伤后）的脆弱性 应激障碍（PTSD）。 Pavlovian调节程序将用于区分“签名跟踪”大鼠 倾向于将高水平的动机意义归因于离散的预测提示，而在很大程度上忽略 上下文，从“目标追踪”大鼠，这些老鼠更多地利用上下文来适当地改变他们的情感 回答。签名跟踪大鼠比目标 - 跟踪器。这些行为特征的神经生物学基础将通过测试之间的差异来探讨 媒体已知的关键边缘电路中功能连接性的签名和目标跟踪器 行为，即从通风海马到伏拟核的途径。神经元活动也将是 使用病毒载体操纵，以测试对条件动机反应的因果影响 食欲和厌恶的提示和上下文。这些实验将检验目标跟踪者的假设 使用从海马输入得出的上下文信息的增加能力来适当修改 对与情感显着事件相关的线索的皮层反应。该项目将训练承诺 科学家并有助于确定成瘾的潜在神经生物学途径，并经常同时发生疾病， 这是一个重要的公共卫生优先事项。