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: 10621835
• 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/10621835
• 关键词: Ablation; Acute; Adult; Affect; Area; Back; Behavior; Brain; Brain region; Cells; Chronic; Code; Cognition; Cues; Cytoplasmic Granules; Data; Dementia; Discrimination; Feedback; Genetic; Head; Hilar; Hippocampus; Image; Impairment; Individual; Interneurons; Knowledge; Learning; Location; Maps; 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; neural; neurogenesis; new therapeutic target; 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.

项目总结