The contribution of adult-born neurons to hippocampal structure and connectivity.

成年神经元对海马结构和连接的贡献。

• 批准号: 7929292
• 负责人: ALEX DRANOVSKY
• 金额: $ 10.71万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7929292
• 关键词: Adult; Affect; Animal Model; Antidepressive Agents; Anxiety; Behavior; Behavioral; Biological; Brain; Brain region; Breeding; Cells; Cellular Structures; Chronic; Complex; Consultations; Cytoplasmic Granules; Distant; Emotional; Environment; Ethical Issues; Exposure to; Fluorescence Microscopy; Fluoxetine; Funding; Genes; Genetic; Genetic Recombination; Goals; Hippocampus (Brain); Homeostasis; Immunohistochemistry; Intervention; Knowledge; Label; Laboratories; Lead; Life; Maintenance; Mentors; Mentorship; Molecular; Molecular Genetics; Mus; Neurobiology; Neurons; Neurosciences Research; Population; Process; Proteins; Psychosocial Stress; Recruitment Activity; Regulation; Reporter; Research; Research Personnel; Research Proposals; Research Training; Retroviridae; Rodent; Role; Science; Series; Social isolation; Stem cells; Stress; Structure; Suid Herpesvirus 1; System; Techniques; Time; Training; Transgenic Mice; Transgenic Organisms; Viral; Wheat Germ Agglutinins; career; dentate gyrus; depressive symptoms; design; experience; granule cell; mature animal; meetings; nerve stem cell; nestin protein; neural circuit; neurogenesis; programs; recombinase; response

DESCRIPTION (provided by applicant): This proposal was designed to prepare the candidate for an independent career in neuroscience research. It includes training and research plans. The training plan combines formal mentorship and consultations, didactics, seminars, and meetings, all designed to provide: 1) expertise in the breeding, maintenance, and characterization of inducible transgenic mice; 2) expertise in molecular and genetic approaches for tracing complex neural circuits from defined populations of neurons; 3) a fund of knowledge in neurobiological issues that will enhance the candidate's ability to think creatively about animal models of psychiatric illness as they pertain to the regulation of neural circuits by stress and the environment; 4) exposure to ethical issues in the responsible conduct of science; and 5) experience in effective laboratory management and mentoring trainees. The research plan entails an analysis of the role of adult-born neurons in hippocampal plasticity. Recent evidence implicates adult hippocampal neurogenesis in response to stress and antidepressant treatment. However, little is known about the contribution of adult-born neurons to the cellular composition of the dentate and to hippocampal projection circuits. In this research proposal, the investigator intends to determine the representation of adult-born neurons within the cellular structure of the dentate gyrus and within hippocampal projections over time. The effects of stress and antidepressant treatment on neuronal turnover and associated projections will also be assessed. Inducible transgenic mice will be used to restrict expression of reporter proteins to neuronal progenitor cells in adult animals. A series of viral and transgenic approaches will be used to restrict expression of trans-synaptic markers to neuronal progenitors. The outlined approaches will allow the investigator to assess how adult-born neurons are represented in the dentate gyrus and in hippocampal connections as a function of time and behavioral/pharmacologic manipulations. Completing the proposed research will define how adult-born neurons contribute to hippocampal plasticity. Completing the training and research plans will lead to establishing the candidate as an independent investigator with expertise in using molecular biological techniques to study how genes and experience modulate complex neural circuits.

描述（由申请人提供）：该提案旨在为候选人做好神经科学研究的独立职业的准备。它包括培训和研究计划。培训计划结合了正式的指导和咨询，教学，研讨会和会议，旨在提供：1）诱导的转基因小鼠的繁殖，维护和表征方面的专业知识； 2）用于追踪明确神经元种群的复杂神经回路的分子和遗传方法的专业知识； 3）神经生物学问题的知识基金将增强候选人对精神病动物模型的创造性思考，因为它们与压力和环境有关神经回路的调节； 4）在负责任的科学行为中暴露于道德问题； 5）有效的实验室管理和指导学员的经验。该研究计划需要分析成年神经元在海马可塑性中的作用。最近的证据表明，对应激和抗抑郁治疗的响应，成年海马神经发生。然而，对于成年出生神经元对齿状齿状细胞组成和海马投射回路的贡献知之甚少。在这项研究建议中，研究人员打算确定齿状回的细胞结构内以及随着时间的推移的海马投影的表示。还将评估压力和抗抑郁药对神经元更新和相关预测的影响。可诱导的转基因小鼠将用于将报告蛋白的表达限制为成年动物中神经元祖细胞的表达。一系列病毒和转基因方法将用于限制反式突触标记的表达对神经元祖细胞。概述的方法将使研究人员能够评估齿状回和海马连接中成人出生的神经元如何作为时间和行为/药理操作的函数。完成拟议的研究将定义成人出生的神经元如何促进海马可塑性。完成培训和研究计划将导致将候选人确立为独立研究者，该研究人员在使用分子生物学技术方面具有专业知识来研究基因和体验如何调节复杂的神经回路。