Role of adult neurogenesis in spatial information encoding in the dentate gyrus

成人神经发生在齿状回空间信息编码中的作用

• 批准号: 10521553
• 负责人: Jose Tiago Goncalves
• 金额: $ 42万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10521553
• 关键词: Ablation; Acute; Address; Adult; Affect; Area; Back; Behavior; Brain; Brain region; Cells; Chronic; Code; Cognition; Cues; Cytoplasmic Granules; Data; Dementia; Discrimination; Feedback; Foundations; Genetic; Head; Hilar; Hippocampus (Brain); Image; Impairment; Individual; Interneurons; Knowledge; Learning; Location; Mediation; Memory; Memory Disorders; Methods; Modeling; Mus; Neurons; Performance; Phase; Play; Population; Process; Role; Specificity; Tactile; Testing; Time; Walking; adult neurogenesis; critical period; dentate gyrus; excitatory neuron; experimental study; granule cell; improved; in vivo; loss of function; neurogenesis; new therapeutic target; relating to nervous system; spatial memory; treadmill; two photon microscopy

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.

项目概要 齿状回 (DG) 是哺乳动物大脑中为数不多的能够持续添加新神经元的区域之一。 成年期。成人神经发生被认为可以通过改善空间和情境记忆来带来优势 歧视：神经发生的丧失会损害区分相似但不同地方的能力，而 提高神经发生率可以提高这种能力。成年出生的神经元，在其发育的关键时期 当它们成熟时，其兴奋性和可塑性增强，被认为可以提高神经的精确度 通过使空间表示更加清晰来在 DG 中进行编码。但目前尚不清楚成年后如何出生 神经元在行为过程中影响 DG 的活动，因为该区域的体内记录最近才成为 可能的。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。为了验证这个假设，我们将使用 2 光子显微镜来 通过神经发生操作对行为小鼠的体内 DG 神经活动进行成像。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会减少空间信息的编码 总干事。 2) 确定成人神经发生率的提高是否足以增加大脑中的空间信息 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 海马苔藓细胞接收来自 DG 颗粒细胞的输入，可能是大脑中的关键电路组件。 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 成人神经发生促进空间记忆过程的基本知识。