Roles for Hippocampal BDNF in the Social Behavior of Mice

描述（由申请人提供）：本指导临床科学家研究职业发展奖（K08）将支持成为基础和转化社会神经科学领域的独立科学家的职业目标。我是一名医学博士，精神病学家博士，埃默里大学精神病学和行为科学助理教授。我也是埃默里转化社会神经科学中心（CTSN）的一名教员。作为一名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，以开发出更好的治疗功能障碍的方法。我对这个K08的短期目标是学习尖端的分子和行为技术，以便研究大脑的社会回路。计划通过课程、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作者。该培训计划将包括：1)在社会神经科学和分子神经科学领域具有杰出综合专业知识的导师；2)在小鼠社会行为分析以及慢病毒、转基因和Cre/Lox方法方面进行培训，以解剖社会认知和行为背后的脑回路；3)埃默里转化社会神经科学中心、冷泉港和威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)参加以社会和分子神经科学为重点的全国性会议；5)参加埃默里大学的助学金写作课程；6)在道德和负责任的研究行为方面进行培训。这项训练计划的科学重点将放在海马BDNF在社会行为中的作用上。海马CA1区的BDNF与社会识别记忆有关，而其在海马CA3区的特定信号则与对其他物种成员的攻击和社会支配有关。我假设CA1中的BDNF对社会识别记忆的巩固及其潜在的结构可塑性至关重要，而CA3中的BDNF对正常水平的攻击和社会支配至关重要。在这个proposal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信号在社会识别记忆巩固中的作用；2）

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.