Analyzing the Role of Adult Hippocampal Neurogenesis in Contextual Fear Memory

描述(由申请者提供)：这个培训和研究奖项将为候选人作为一名分子和行为神经学家的独立职业生涯做好准备，使用严格的行为测试和基因操作来分析潜在的学习和记忆的大脑回路。应聘者是一位在动物学习领域拥有丰富经验的实验心理学家。该奖项提供的培训在哥伦比亚大学精神病学和神经科学系进行，将使应聘者能够(1)发展分子遗传学和定量显微镜方面的实验室技能；(2)扩大他在分子遗传学和翻译神经科学方面的知识，使他能够独立开发新的科学想法，将他的研究成果与现有知识结合起来，并将其与临床实践相结合；(3)在专业发展方面接受指导；以及(4)对科学实践中固有的伦理问题产生深刻的理解。培训目标将通过实践培训、正式指导、与经验丰富的独立研究人员的咨询、课程作业、研讨会出席和专业科学会议相结合的计划来实现。该奖项支持的研究将阐明成年海马区神经发生有助于学习和记忆的机制。成年海马体保留了产生神经元的能力，而且迅速增长的文献证明，成年出生的神经元在功能上具有重要意义。例如，这位候选人已经证明，使用辐射或可诱导的遗传方法阻止海马神经发生会损害背景恐惧条件反射，这是一种普遍存在的学习形式，在这种学习中，有机体会对预测伤害的环境产生恐惧。以情景恐惧条件作用作为模型系统，这项拟议的研究将使用靶向照射和遗传操作来分析成年出生的神经元如何对记忆的获取、保持和提取做出贡献。这项拟议的研究将为研究成年出生的神经元在学习和行为中的作用开发新的工具，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变化如何有助于情感障碍的病因或治疗。

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.