Analyzing the Role of Adult Hippocampal Neurogenesis in Contextual Fear Memory

分析成人海马神经发生在情境恐惧记忆中的作用

• 批准号: 8326534
• 负责人: MICHAEL R DREW
• 金额: $ 24.22万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-25 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326534
• 关键词: Ablation; Adult; Affect; Age; Animals; Antidepressive Agents; Area; Award; Behavior; Behavioral; Behavioral Genetics; Biological Models; Biology; Brain; Cell Proliferation; Cells; Consultations; Cranial Irradiation; Cytoplasmic Granules; Data; Development; Diphtheria Toxin; Dose; Drug effect disorder; Emotional disorder; Environment; Ethical Issues; Etiology; Exhibits; Fright; Genetic; Goals; Hippocampus (Brain); Immediate-Early Genes; Impairment; Knowledge; Laboratories; Learning; Life; Literature; Memory; Mentorship; Methods; Molecular; Molecular Genetics; Mus; Neurons; Neurosciences; Organism; Performance; Physiologic pulse; Procedures; Process; Psychiatry; Psychologist; Quantitative Microscopy; Research; Research Personnel; Research Support; Research Training; Retrieval; Rodent; Role; Science; Shock; Staging; Synapses; System; Testing; Therapeutic; Time; Toxin; Training; Universities; Wild Type Mouse; adult neurogenesis; aged; base; behavior test; career; classical conditioning; clinical practice; cohort; conditioned fear; conditioning; diphtheria toxin receptor; experience; genetic manipulation; insight; irradiation; killings; meetings; memory acquisition; memory process; memory retrieval; neurogenesis; novel; programs; promoter; recombinase; research study; response; skills; tool; translational neuroscience; young adult

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.

描述（由申请人提供）：该培训和研究奖项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。候选人是一位实验心理学家，在动物学习领域拥有丰富的经验。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，将使候选人能够（1）发展分子遗传学和定量显微镜方面的实验室技能； （2）拓展分子遗传学和转化神经科学知识，使其能够独立发展新颖的科学思想，将研究成果与现有知识相结合，并将其与临床实践联系起来； (3) 接受专业发展指导； (4) 对科学实践中固有的伦理问题有深刻的理解。培训目标将通过结合实践培训、正式指导、经验丰富的独立研究人员咨询、课程作业、参加研讨会和专业科学会议的计划来实现。该奖项支持的研究将阐明成人海马神经发生促进学习和记忆的机制。成年海马体保留了生成神经元的能力，并且快速增长的文献证明，成年神经元具有重要的功能。例如，该候选人表明，使用辐射或诱导遗传方法阻断海马神经发生会损害情境恐惧调节，这是一种普遍存在的学习形式，在这种学习形式中，生物体获得了对预测伤害的环境的恐惧。拟议的研究将使用情境恐惧调节作为模型系统，利用定向照射和基因操作来分析成年神经元如何有助于记忆的获取、保留和检索。拟议的研究将开发新的工具来研究成年神经元在学习和行为中的作用，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促进病因或治疗情绪障碍。

项目成果

Characterization of the role of adult neurogenesis in touch-screen discrimination learning.

• DOI: 10.1002/hipo.22337
• 发表时间: 2014-12
• 期刊: HIPPOCAMPUS
• 影响因子: 3.5
• 作者: Swan, Alicia A.;Clutton, Jonathan Edward;Chary, Priyanka Kesavan;Cook, Sarah G.;Liu, Grace G.;Drew, Michael R.
• 通讯作者: Drew, Michael R.

Behavioral experience induces zif268 expression in mature granule cells but suppresses its expression in immature granule cells.

• DOI: 10.3389/fnsys.2015.00118
• 发表时间: 2015
• 期刊: Frontiers in systems neuroscience
• 影响因子: 3
• 作者: Huckleberry KA;Kane GA;Mathis RJ;Cook SG;Clutton JE;Drew MR
• 通讯作者: Drew MR