Identification of Neural and Molecular Mechanisms of Infant Social Fear Learning

 描述（由申请人提供）：临床研究报告称，恐惧情绪创伤可能会代代相传。父母有创伤后应激障碍（PTSD）病史会增加孩子患PTSD的风险，而父母有特定恐惧症病史会增加后代患恐惧症的风险。现有研究表明，社会学习和记忆机制参与了创伤的代际传递。这项工作旨在了解婴儿期社会恐惧学习的神经生物学。我的目标是深入了解早期婴儿社会恐惧学习的电路和分子机制，以开发新的预防和治疗方法，防止创伤在几代人中永久存在。 指导这项工作的首要假设是，社会恐惧学习机制参与了婴儿期父母对婴儿的恐惧反应传递。我建议在大鼠模型中研究婴儿期社会恐惧学习的神经生物学， 识别和实验测试参与社会传播的威胁反应形成的潜在神经和分子通路的手段。这一提议的核心假设是 婴儿期的社会恐惧学习与杏仁核中催产素（OT）信号的表观遗传改变有关。提出了两个具体目标来检验总体和中心假设：1）确定下丘脑-杏仁核神经通路在婴儿期母性恐惧传递中的作用，2）确定表观遗传学改变的作用 恐惧的母婴社会传递过程中婴儿杏仁核中的OT能系统。 作为一名学术儿童和青少年精神病学家，我对儿童早期创伤和焦虑症有临床和研究兴趣。作为密歇根大学的一名教师，我的临床专业是治疗患有焦虑症的儿童，以及在围产期治疗女性（其中许多人有情感创伤和创伤后应激障碍的历史）。我的研究项目将研究儿童早期创伤的电路和分子机制以及婴儿期创伤的代际传递。分子和行为神经科学研究所和精神病学系拥有世界一流的师资和设施。特别是，我将受益于深思熟虑的，“动手”的指导和指导经验丰富的科学家和临床医生谁深深致力于我未来的学术和研究成功。

 DESCRIPTION (provided by applicant): Clinical studies report that fear emotional trauma may be transmitted across generations. Parental history of posttraumatic stress disorder (PTSD) increases the child's risk of developing PTSD, whereas parental history of a specific phobia increases the risk of phobia in the offspring. Existing research suggests that social learning and memory mechanisms are involved in the intergenerational transmission of trauma. This work aims to understand the neurobiology of social fear learning in infancy. My goal is to gain insight into the circuit and molecular mechanisms of early infant social fear learning in order to develop novel preventive and therapeutic approaches that could prevent the perpetuation of trauma across generations. The overarching hypothesis that guides this work is that social fear learning mechanisms are involved in the parent-to-infant transmission of fear responses in infancy. I propose to study the neurobiology of social fear learning in infancy in a rat model as a means to identify and experimentally test potential neural and molecular pathways involved in the formation of socially transmitted threat responses. The central hypothesis for this proposal is that social fear learning in infancy is associated with epigenetic alterations of oxytocin (OT) signaling in the amygdala. Two specific aims are proposed to test the overarching and central hypotheses: 1) to determine the role of the hypothalamus-amygdala neural pathway in the transmission of maternal fear in infancy, 2) to determine the role of epigenetic alterations of the OT-ergic system in the infant's amygdala during the mother to infant social transmission of fear. As an academic child and adolescent psychiatrist, I have clinical and research interests in early childhood trauma and anxiety disorders. As a faculty member at the University of Michigan, my clinical specialty is treating children with anxiety disorders, as well as treating women (many of them with a history of emotional trauma and PTSD) during the perinatal period. My research program will study the circuit and molecular mechanisms of early childhood trauma and intergenerational transmission of trauma in infancy. The Molecular and Behavioral Neuroscience Institute and the Department of Psychiatry have a world-class faculty and facilities. In particular, I will benefit from thoughtful, 'hands-on' mentoring and instruction by experienced scientists and clinicians who are deeply committed to my future academic and research success.