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

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，所有这些都是为了提供：1)可诱导转基因小鼠的培育、维护和特性方面的专业知识；2)分子和遗传方法方面的专业知识，用于从特定的神经元群体中追踪复杂的神经回路；3)神经生物学问题的知识基金，将增强候选人创造性地思考精神疾病动物模型的能力，因为这些模型与应激和环境对神经回路的调节有关；4)在负责任的科学行为中接触伦理问题；以及5)有效的实验室管理和指导受训人员的经验。该研究计划需要分析成年出生的神经元在海马可塑性中的作用。最近的证据表明，成年海马区的神经发生与应激和抗抑郁治疗有关。然而，关于成年出生的神经元对齿状回的细胞组成和对海马体投射回路的贡献，人们知之甚少。在这项研究计划中，研究人员打算确定成年出生的神经元在齿状回的细胞结构中和随着时间的推移在海马区投射中的代表性。应激和抗抑郁治疗对神经元周转和相关投射的影响也将被评估。可诱导的转基因小鼠将被用来限制报告蛋白在成年动物的神经前体细胞中的表达。将使用一系列病毒和转基因方法将跨突触标记的表达限制在神经元前体细胞上。概述的方法将使研究人员能够评估成年出生的神经元在齿状回和海马区连接中的表现，作为时间和行为/药物操作的函数。完成这项拟议的研究将确定成年出生的神经元如何对海马可塑性做出贡献。完成培训和研究计划将使候选人成为一名独立的研究员，拥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。

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.