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.

项目概要/摘要 该提案旨在为通过 NIDA 夏季项目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识别常见的神经生物学底物。 这可能会使人容易上瘾，并且容易患上经常并发的疾病，例如创伤后综合症 应激障碍（PTSD）将被用来区分“体征追踪”大鼠。 倾向于将高水平的动机意义归因于离散的预测线索，而很大程度上忽略了 背景，来自“目标跟踪”老鼠，它们更多地利用背景来适当地调整他们的情绪 与目标反应相比，信号追踪大鼠更容易出现提示引发的成瘾和创伤后应激障碍（PTSD）行为。 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索。 已知调节动机的关键边缘回路内功能连接的标志和目标跟踪器 行为，即从腹侧海马到伏隔核的神经元活动也将发生变化。 使用病毒载体进行操作，以测试对条件动机反应的因果影响 这些实验将检验目标追踪器所具有的假设。 使用来自海马输入的上下文信息进行适当修改的能力增强 该项目将训练一个有前途的人对与情感显着事件相关的线索的皮层反应。 科学家并帮助阐明成瘾和经常发生的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。