Analyzing the Role of Adult Hippocampal Neurogenesis in Contextual Fear Memory

描述（由申请人提供）：这项培训和研究奖励将为候选人作为分子和行为神经科学家的独立职业做好准备，使用严格的行为测试和基因操作来分析学习和记忆背后的大脑回路。候选人是一名实验心理学家，在动物学习领域有丰富的经验。该奖项提供的培训将在哥伦比亚大学精神病学和神经科学部门进行，并将使候选人能够(1)发展分子遗传学和定量显微镜的实验室技能；(2)拓展分子遗传学和转化神经科学的知识，能够独立发展新的科学思想，将研究成果与现有知识相结合，并与临床实践相结合；(3)接受专业发展指导；(4)培养对科学实践中固有的伦理问题的深刻理解。培训目标将通过实践培训、正式指导、与有经验的独立研究人员的咨询、课程、研讨会出席和专业科学会议相结合的项目来实现。该奖项支持的研究将阐明成人海马神经发生有助于学习和记忆的机制。成人海马体保留了产生神经元的能力，越来越多的文献表明，成人出生的神经元具有重要的功能。例如，候选人已经证明，使用辐射或诱导遗传方法阻止海马神经发生会损害情境恐惧条件反射，这是一种普遍存在的学习形式，生物体在这种学习形式中获得对预测危害的环境的恐惧。利用情境恐惧条件反射作为模型系统，本研究将使用靶向照射和基因操作来分析成人出生的神经元如何促进记忆的获取、保留和检索。这项研究将为研究成人神经元在学习和行为中的作用开发新的工具，进一步加深我们对记忆生物学的理解，并可能深入了解神经发生的改变如何影响病因或治疗情绪障碍。

DESCRIPTION (provided by applicant): This training and research award will prepare the candidate for an independent career as a molecular and behavioral neuroscientist using rigorous behavioral testing and genetic manipulations to analyze the brain circuits underlying learning and memory. The candidate is an experimental psychologist with significant experience in the area of animal learning. Training provided under the award take place at Columbia University's Departments of Psychiatry and Neuroscience and will enable the candidate to (1) develop laboratory skills in molecular genetics and quantitative microscopy; (2) expand his knowledge of molecular genetics and translational neuroscience so that he can independently develop novel scientific ideas, integrate his research findings with existing knowledge, and relate them to clinical practice; (3) receive mentorship in professional development; and (4) develop a strong understanding of the ethical issues inherent in the practice of science. The training goals will be accomplished through a program combining practical training, formal mentorship, and consultations with experienced independent researchers, coursework, seminar attendance, and professional scientific meetings. The research supported under the award will elucidate mechanisms through which adult hippocampal neurogenesis contributes to learning and memory. The adult hippocampus retains the ability to generate neurons, and a rapidly growing literature documents that adult-born neurons are functionally significant. The candidate has shown, for instance, that blocking hippocampal neurogenesis using irradiation or an inducible genetic method impairs contextual fear conditioning, a ubiquitous form of learning in which organisms acquire fear of environments that predict harm. Using contextual fear conditioning as a model system, the proposed research will use targeted irradiation and genetic manipulations to analyze how adult-born neurons contribute to acquisition, retention, and retrieval of memories. The proposed research will develop new tools for studying the role of adult-born neurons in learning and behavior, further our understanding of the biology of memory, and may give insight into how alterations in neurogenesis contribute to the etiology or treatment emotional disorders.