Harnessing Adult Hippocampal Neurogenesis to Enhance Learning and Modulate Mood

这个项目的目标是了解如何利用成年出生的神经元的可塑性来 调整学习和情绪调节。在奖项的培训阶段(K99)，候选人 增强了他在发育神经生物学、分子生物学和 小鼠遗传学，在行为神经科学方面接受过严格的训练，用于研究认知和 老鼠的情绪。候选人使用了一种新的遗传函数增益方法来证明 选择性增加成年海马区神经发生对认知和情绪的影响。在 独立(Roo)阶段，候选人将探索操纵成年出生的属性的效果 齿状回依赖功能的是齿状颗粒神经元，而不是它们的数量。候选人 将以最近的工作为基础，表明转录因子Kruppel样因子9调节齿状颗粒 神经元成熟。这些特定的目标将评估Kruppel样因子9的遗传过度表达在 成体神经干细胞和齿状颗粒神经元对其成熟和海马区功能的影响 在正常小鼠和抑郁症小鼠模型中。尽管越来越多的文献记录了独特的 新神经元的特性，新神经元的这些特性如何与基本助记符相关 诸如模式分离和齿状回在情绪调节中的作用等过程很差 明白了。因此，这里提出的实验将尝试将离散的变化与 具有电路功能和行为的单元类型属性。

The goal of this project is to understand how the plasticity of adult-born neurons may be harnessed to modify learning and mood regulation. During the training phase (K99) of the award, the candidate augmented his extensive background experience in developmental neurobiology, molecular biology and mouse genetics with a rigorous training in behavioral neuroscience as applied to the study of cognition and emotion in mice. The candidate employed a novel genetic gain of function approach to demonstrate the impact of selectively increasing adult hippocampal neurogenesis on cognition and mood. In the independent (ROO) phase, the candidate will explore the effects of manipulating the properties of adult-born dentate granule neurons, rather than their number, on dentate gyrus dependent functions. The candidate will build on recent work showing that the transcription factor Kruppel-like factor 9 regulates dentate granule neuronal maturation. The Specific Aims will assess how genetic over expression of Kruppel-like factor 9 in adult neural stem cells and dentate granule neurons influences their maturation and hippocampal functions in normal mice and mouse models of depression. Although a growing literature documents the unique properties of new neurons, how these properties of new neurons relate to fundamental mnemonic processes such as pattern separation and the role of the dentate gyrus in mood regulation is poorly understood. Therefore, the experiments proposed here will attempt to causally link discrete changes in cell-type properties with circuit functions and behavior.