Role of Adult Neurogenesis in Spatial Information Encoding in the Dentate Gyrus

项目摘要 齿状回（DG）是少数几个通过大脑皮层持续增加新神经元的哺乳动物大脑区域之一。 成年成人神经发生被认为通过改善空间和背景记忆来赋予优势 辨别力：神经发生的丧失损害了辨别相似但不同部位的能力， 提高神经发生的速率改善了这种能力。成年人出生的神经元，在他们生命的关键时期， 当它们具有增强的兴奋性和可塑性时，成熟被认为可以提高神经元的精确性。 通过使空间表示更加独特来在DG中进行编码。然而，目前尚不清楚成年人如何出生 神经元在行为过程中影响DG的活性，因为在该区域的体内记录最近才成为 可能我们假设成人神经发生通过增加空间信息来改善空间记忆 由DG通过本地反馈网络进行编码。为了验证这一假设，我们将使用双光子显微镜， 在具有神经发生操作行为小鼠体内成像DG神经活性。我们的目标是：1）确定 如果成年神经发生的耗竭或新神经元的沉默减少了空间信息的编码， 的DG。2)确定成人神经发生的增强速率是否足以增加空间信息， DG以及这些变化是否需要新神经元的活动，以及3）确定是否 海马苔藓细胞，从DG颗粒细胞接收输入，可能是一个关键的电路组成部分， 介导DG空间信息的神经发生依赖性变化。从这些实验中，我们将获得 对成人神经发生促进空间记忆过程的基本知识。

Project Summary The dentate gyrus (DG) is one of the few mammalian brain regions that continue to add new neurons through adulthood. Adult neurogenesis is thought to confer advantages by improving spatial and context memory discrimination: loss of neurogenesis impairs the ability to discriminate between similar but distinct places while enhancing rates of neurogenesis improves this ability. Adult-born neurons, during a critical time in their maturation when they have enhanced excitability and plasticity, are thought to improve the precision of neural coding in the DG by making spatial representations more distinct. However, it is not yet known how adult-born neurons affect the activity of the DG during behavior, as in vivo recordings in this area have only recently become possible. We hypothesize that adult neurogenesis improves spatial memory by increasing the spatial information encoded by the DG, via local feedback networks. To test this hypothesis we will use 2-photon microscopy to image DG neural activity in vivo in behaving mice with manipulations of neurogenesis. We aim to: 1) Determine if depletion of adult neurogenesis or silencing of new neurons decreases the encoding of spatial information in the DG. 2) Determine if enhancing rates of adult neurogenesis is sufficient to increase spatial information in the DG and whether the activity of new neurons is required for these changes, and 3) determine whether hippocampal mossy cells, which receive inputs from DG granule cells, may be a critical circuit component in the mediation of neurogenesis-dependent changes to DG spatial information. From these experiments, we will gain essential knowledge of the processes through which adult neurogenesis contributes to spatial memory.