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: 7339810
• 负责人: ALEX DRANOVSKY
• 金额: $ 17.69万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-11 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7339810
• 关键词: Adult; Affect; Animal Model; Antidepressive Agents; Anxiety; Behavior; Behavioral; Biological; Brain; Brain region; Breeding; Cells; Cellular Structures; Chronic; Chronic stress; 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; Personal Satisfaction; 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; Synapses; System; Techniques; Thinking; Time; Training; Transgenic Mice; Transgenic Organisms; Viral; Wheat Germ Agglutinins; career; dentate gyrus; depressive symptoms; design; experience; granule cell; mature animal; 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）：本提案旨在为候选人在神经科学研究领域的独立职业生涯做好准备。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，所有这些都旨在提供：1)可诱导转基因小鼠的育种、维护和表征方面的专业知识；2)在分子和遗传方法方面的专业知识，用于从确定的神经元群体中追踪复杂的神经回路；3)在神经生物学问题方面的知识储备将增强候选人创造性思考精神疾病动物模型的能力，因为它们与压力和环境对神经回路的调节有关；4)在负责任的科学行为中暴露伦理问题；5)有有效的实验室管理和指导学员的经验。这项研究计划需要分析成年神经元在海马可塑性中的作用。最近的证据暗示成人海马神经发生在应激反应和抗抑郁治疗。然而，对于成年出生的神经元对齿状和海马投射回路的细胞组成的贡献知之甚少。在这项研究计划中，研究者打算确定成年出生的神经元在齿状回细胞结构和海马投影中的表现。应激和抗抑郁治疗对神经元周转和相关预测的影响也将被评估。可诱导的转基因小鼠将用于限制成年动物神经元祖细胞中报告蛋白的表达。一系列的病毒和转基因方法将被用来限制跨突触标记在神经元祖细胞中的表达。概述的方法将允许研究者评估成年出生的神经元如何作为时间和行为/药物操作的函数在齿状回和海马连接中表现出来。完成拟议的研究将确定成年出生的神经元如何对海马体可塑性做出贡献。完成培训和研究计划将使候选人成为一名独立的研究者，具有使用分子生物学技术研究基因和经验如何调节复杂神经回路的专业知识。