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

描述（由申请人提供）：该提案旨在为候选人在神经科学研究中的独立职业做准备。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，所有这些都旨在提供：1）诱导型转基因小鼠的繁殖，维护和表征方面的专业知识; 2）分子和遗传方法的专业知识，用于从确定的神经元群体中追踪复杂的神经回路; 3）神经生物学问题的知识基金，这将提高候选人创造性地思考精神疾病动物模型的能力，因为它们涉及压力和环境对神经回路的调节; 4）在负责任的科学行为中接触伦理问题; 5）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神经发生对应激和抗抑郁治疗的反应。然而，很少有人知道的贡献成年出生的神经元的细胞组成的齿状回和海马投射电路。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和海马投射内随时间的代表性。还将评估应激和抗抑郁药治疗对神经元更新和相关预测的影响。诱导型转基因小鼠将用于将报告蛋白的表达限制于成年动物的神经元祖细胞。一系列的病毒和转基因方法将被用来限制表达的跨突触标记的神经元祖细胞。概述的方法将允许研究者评估成年出生的神经元如何在齿状回和海马连接中作为时间和行为/药理学操作的函数。完成拟议的研究将确定成年出生的神经元如何有助于海马可塑性。完成培训和研究计划将导致建立候选人作为一个独立的研究人员，在使用分子生物学技术的专业知识，研究基因和经验如何调节复杂的神经回路。

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.