Roles for Hippocampal BDNF in the Social Behavior of Mice

描述(由申请者提供)：这个有指导的临床科学家研究职业发展奖(K08)将支持成为基础和翻译社会神经科学领域的独立科学家的职业目标。我是埃默里大学精神病学和行为科学的医学博士、博士和助理教授。我也是埃默里翻译社会神经科学中心(CTSN)的教员。作为一名获得委员会认证的精神病学家，我的目标是研究调节社会行为的大脑系统，以开发出改善其功能障碍的治疗方法。我对这款K08的短期目标是学习尖端的分子和行为技术，这将有助于研究大脑的社会回路。计划通过课程作业、研讨会和国家会议进一步推进我在社会和分子神经科学方面的教育，并成为一名专家拨款撰稿人。这项培训计划将包括：1)指导，他们在社会和分子神经科学方面拥有杰出的综合专长；2)在小鼠的社会行为分析以及慢病毒、转基因和CRE/Lox方法方面的动手培训，以剖析潜在的社会认知和行为的脑电路；3)通过埃默里翻译社会神经科学中心、冷泉港和惠康信托社会认知生物学暑期学校提供的社会和分子神经科学课程；4)出席侧重于社会和分子神经科学的国家会议；5)参加埃默里大学提供的拨款撰写课程；6)进行伦理和负责任的研究工作培训。这项训练计划的科学重点将放在海马区BDNF在社会行为中的作用。海马区CA1区的脑源性神经营养因子与社会再认记忆有关，而其在海马区CA3区的特异信号与攻击其他物种成员和社会优势有关。我推测，CA1中的BDNF对巩固社会识别记忆及其潜在的结构可塑性至关重要，而CA3中的BDNF对于正常水平的攻击性和社会优势是必不可少的。在这个提议中，我将学习新的转基因小鼠技术，同时直接测试这些关于BDNF信号在海马体功能和社会认知和行为中的作用的假设。我的研究将：1)直接测试BDNF信号在巩固社会再认记忆中的作用；2) 直接测试海马区BDNF对社会行为的重要性；3)检测TrkB激动剂对社会功能障碍小鼠模型的影响。这项工作具有创新性，因为海马区BDNF对社会认知和行为的影响还没有得到很好的研究。这项建议将建立在我在分子和组织学方法方面的背景基础上，同时推进我在社会神经科学方法和最新的分子神经科学技术方面的教育。该项目将与CTSN的理念很好地结合在一起，CTSN强调动物模型为临床实践提供信息的重要性，其目标是以一种协作和跨学科的方法来研究社会行为的神经生物学。

DESCRIPTION (provided by applicant): This Mentored Clinical Scientist Research Career Development Award (K08) will support a career goal of becoming an independent scientist within the field of basic and translational social neuroscience. I am an MD,PhD psychiatrist and Assistant Professor in Psychiatry and Behavioral Science at Emory University. I am also a faculty member in the Emory Center for Translational Social Neuroscience (CTSN). My goal as a board certified psychiatrist is to study brain systems regulating social behaviors to develop improved treatments for their dysfunction. My short-term goals for this K08 are to learn cutting-edge molecular and behavioral techniques that will allow for studying the brain's social circuits. plan to further advance my education in social and molecular neuroscience through coursework, workshops and national meetings, and to become an expert grant writer. This training plan will include: 1) mentorship from, who have an outstanding range of combined expertise in social and molecular neuroscience; 2) hands on training in social behavioral assays in mice and in lentiviral, transgenic and Cre/Lox methods to dissect brain circuitry underlying social cognition and behavior; 3) coursework in social and molecular neuroscience offered through the Emory Center for Translational Social Neuroscience, Cold Springs Harbor and The Wellcome Trust Summer School on the Biology of Social Cognition; 4) attendance at national meetings that have a focus on social and molecular neuroscience; 5) participation in grant writing courses offered at Emory University; 6) training in the ethical and responsible conduct of research. This scientific focus of this training plan will be on the role of hippocampal BDNF in social behavior. BDNF in the hippocampal CA1 region is implicated in social recognition memory, while its specific signaling in the hippocampal CA3 region is implicated in aggression towards other species members and social dominance. I hypothesize that BDNF in CA1 is critical to the consolidation of social recognition memory and to its underlying structural plasticity, while BDNF in CA3 is essential for normal levels of aggression and social dominance. In this proposal I will learn novel transgenic mouse technology while directly testing these hypotheses regarding the role of BDNF signaling in hippocampal function and social cognition and behavior. My research will: 1) directly test the role of BDNF signaling in consolidation of social recognition memory; 2) directly test the importance of BDNF in hippocampal regions to social behavior; 3) examine the effects of TrkB agonist treatment on mouse models of social impairment. This work is innovative because the impact of hippocampal BDNF on social cognition and behavior has not been well explored. This proposal will build on my background in molecular and histological methods while advancing my education in social neuroscience methods and in the most current molecular neuroscience techniques. This project will integrate well with the philosophy of the CTSN, which emphasizes the importance of animal models to inform clinical practice, and whose aim is a collaborative and interdisciplinary approach to studying the neurobiology of social behavior.