Neural Circuitry of Shared Vulnerability to Both PTSD and Addiction

创伤后应激障碍和成瘾的共同脆弱性的神经回路

• 批准号: 9273501
• 负责人: Jonathan David Morrow
• 金额: $ 19.66万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9273501
• 关键词: Address; Afghanistan; Amygdaloid structure; Anesthesiology; Animal Housing; Animal Model; Area; Aversive Stimulus; Basic Science; Behavior; Behavioral; Biological Neural Networks; Biomedical Engineering; Brain region; Brain-Derived Neurotrophic Factor; Clinic; Clinical; Cocaine; Comorbidity; Complex; Corpus striatum structure; Cues; Desire for food; Diagnostic; Disease; Doctor of Medicine; Doctor of Philosophy; Early identification; Emotional; Environment; Funding; Gene Expression; Goals; Health; Histology; Immediate-Early Genes; Immunohistochemistry; Individual; Individual Differences; Injection of therapeutic agent; Institutes; Iraq; Knowledge; Learning; Measures; Medial; Mediating; Mental disorders; Mentors; Michigan; Microinjections; Microscopy; Mission; Molecular; Motivation; National Institute of Drug Abuse; Negative Valence; Neurobiology; Neurons; Neurosciences; Nucleus Accumbens; Pathway interactions; Patients; Pattern; Phenotype; Physicians; Population; Positive Valence; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevention strategy; Procedures; Process; Program Development; Psychiatry; Psychology; Radiology Specialty; Rattus; Regulation; Relapse; Research; Research Personnel; Research Project Grants; Residencies; Resistance; Resources; Rewards; Scientist; Self Administration; Services; Stimulus; Structure; Substance Use Disorder; Techniques; Testing; Time; Training; Training Programs; Training and Education; Translational Research; United States National Institutes of Health; Universities; Veterans; Viral Vector; Work; addiction; behavior test; behavioral study; career; clinical practice; conditioned fear; design; dual diagnosis; effective therapy; emotional behavior; experience; experimental study; mid-career faculty; neural circuit; neuromechanism; optogenetics; pre-clinical; professor; psychologic; public health priorities; public health relevance; response; skills; tool; trait; treatment response

DESCRIPTION (provided by applicant): This K08 proposal describes a 5-year training program for the development of an academic career in addiction research. The candidate completed his M.D. and Ph.D. in Neuroscience, and then went on to complete a structured residency in Psychiatry at the University of Michigan. He was recently appointed Assistant Professor of Psychiatry at University of Michigan, where in addition to basic research he now treats patients with substance use disorders at the Addiction Treatment Services clinic. The candidate's education and training in both neuroscience and psychiatry have prepared him well for this project, and he will now expand on his scientific skills through a unique integration of interdepartmental resources. To achieve full research independence, he has identified three key Training Objectives: (1) to gain proficiency in advanced neuroanatomical techniques, particularly immunohistochemistry, (2) to gain expertise in microinjections and the use of viral vectors to experimentally manipulate behavior, and (3) to learn how to use optogenetics as a tool for interrogating neural circuits that influence specific behaviors. The proposed K08 project will take place within the Department of Psychiatry and the Molecular & Behavioral Neuroscience Institute at the University of Michigan. The Department and Institute benefit from close collaborative relationships with other units including Bioengineering, Psychology, Radiology, and the CTSA- funded Michigan Institute for Clinical and Health Research. This vigorous research environment includes ample access to behavioral testing facilities, histology and microscopy resources, and animal housing, and it nurtures an expanding group of translational psychiatric researchers. The primary mentor, Terry Robinson PhD, is a productive and well-funded neuroscientist who has more than 30 years of experience with basic addiction research, and an established track record of mentoring junior investigators. The candidate will also benefit from two local co-mentors, Stanley Watson MD PhD, who pioneered the use of immunohistochemistry to study emotional behavior and has mentored several successful physician-scientists over his 30+ years of research, and Gina Poe PhD, an Associate Professor of Anesthesiology who has expertise in the use of optogenetics to study behavior in rats. Pedro Lowenstein MD PhD is an experienced consultant on this project with considerable expertise in viral vectors and translational research. The research project focuses on identifying common neurobiological substrates that confer vulnerability both to addiction and to frequently co-occurring disorders such as post-traumatic stress disorder. This will be accomplished by identifying neural circuits responsible for generating excessive emotional and motivational responses to both appetitive and aversive conditioned cues. The specific aims include: 1) identifying areas of overlap in the neurons and circuits activated by both appetitive and aversive conditioned cues, 2) testing whether increasing connectivity within limbic circuitry can simultaneously reduce both conditioned approach and conditioned fear, and 3) using optogenetics to identify specific pathways that exert inhibitory control over both appetitive and aversive motivational responses. The proposed K08 project is well-aligned with the missions of the NIH and NIDA. The project will train a promising scientist and help clarify neurobiological pathways to addiction and frequently co-occurring disorders, which is a significant public health priority.

描述（由申请人提供）：本 K08 提案描述了一项为期 5 年的培训计划，旨在发展成瘾研究的学术生涯。候选人完成了医学博士和博士学位。获得神经科学博士学位，然后继续在密歇根大学完成精神病学的结构化住院实习。他最近被任命为密歇根大学精神病学助理教授，除了基础研究外，他现在还在成瘾治疗服务诊所治疗患有物质使用障碍的患者。该候选人在神经科学和精神病学方面的教育和培训使他为这个项目做好了充分的准备，他现在将通过独特的跨部门资源整合来扩展他的科学技能。为了实现完全的研究独立性，他确定了三个关键的培训目标：(1) 熟练掌握先进的神经解剖技术，特别是免疫组织化学，(2) 获得显微注射和使用病毒载体实验操纵行为的专业知识，(3) 学习如何使用光遗传学作为询问影响特定行为的神经回路的工具。拟议的K08项目将采取 密歇根大学精神病学系和分子与行为神经科学研究所。该系和研究所受益于与其他单位的密切合作关系，包括生物工程、心理学、放射学和 CTSA 资助的密歇根临床与健康研究所。这种充满活力的研究环境包括充足的行为测试设施、组织学和显微镜资源以及动物住房，并培养了越来越多的转化精神病学研究人员。主要导师 Terry Robinson 博士是一位多产且资金充足的神经科学家，在基础成瘾研究方面拥有 30 多年的经验，并在指导初级研究人员方面拥有良好的记录。该候选人还将受益于两位当地的共同导师：斯坦利·沃森医学博士，他率先使用免疫组织化学来研究情绪行为，并在 30 多年的研究中指导了几位成功的医师科学家；吉娜·坡博士，麻醉学副教授，拥有利用光遗传学研究大鼠行为的专业知识。 Pedro Lowenstein 医学博士是该项目的一位经验丰富的顾问，在病毒载体和转化研究方面拥有丰富的专业知识。该研究项目的重点是确定常见的神经生物学底物，这些底物会导致成瘾和经常发生的疾病（例如创伤后应激障碍）的脆弱性。这将通过识别负责对食欲和厌恶条件暗示产生过度情绪和动机反应的神经回路来实现。具体目标包括：1）确定由食欲和厌恶条件性线索激活的神经元和回路中的重叠区域，2）测试增加边缘回路内的连接是否可以同时减少条件性接近和条件性恐惧，以及3）使用光遗传学来识别对食欲和厌恶动机反应施加抑制控制的特定途径。拟议的 K08 项目与 NIH 和 NIDA 的使命非常契合。该项目将培训一位有前途的科学家，并帮助阐明成瘾和经常并发疾病的神经生物学途径，这是一个重要的公共卫生优先事项。