OPTOGENETIC MAPPING OF CELL SPECIFIC CONNECTIONS IN THE MOUSE BRAIN AFTER STROKE

中风后小鼠大脑中细胞特异性连接的光遗传学图谱

基本信息

  • 批准号:
    10201764
  • 负责人:
  • 金额:
    $ 41.89万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-30 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT The goal of the current proposal is to determine how molecular- and systems-level mechanisms of brain repair interact to influence behavioral recovery after focal ischemia in mice. Stroke causes direct structural damage to local circuits and indirect functional damage to global networks that can result in behavioral deficits spanning multiple domains. Neuroplasticity after stroke involves molecular changes within perilesional tissue that can be influenced by distant regions spared from injury. At the systems level, functional magnetic resonance imaging has revealed that recovery from stroke is associated with functional reorganization of the brain through the formation of new or alternative circuits. Directly impacted brain regions remap to adjacent tissue in concert with behavioral recovery. More globally, patterns of resting-state functional connectivity gradually normalize in patients experiencing good recovery. While functional neuroimaging studies in humans and animal models consistently demonstrate local and global changes in functional brain organization after stroke, it is unknown how these processes interrelate to support behavioral recovery. Understanding how (or if) remapped brain regions reintegrate into global networks to support recovery after stroke requires more direct examination of evolving local and global connectivity structure. At the molecular level, limited data suggest that new axons appear after stroke in periinfarct cortex and distant, homotopic contralateral cortex. Increased expression of plasticity-associated genes are found in perilesional tissue including those involved in axonal sprouting. Growth Associated Protein 43 (GAP-43) is an integral membrane protein found in axonal growth cones, synapses, and widely induced after focal ischemia. This protein might drive anatomical connections within the periinfarct that support functional restoration after stroke. However, the role of axonal sprouting in functional neuroplasticity following focal ischemia has not been examined. We hypothesize that GAP-43-dependent axonal sprouting is required for local circuit repair and reintegration into global networks, and this evolving process drives the degree of behavioral recovery after stroke. We further hypothesize that axonal sprouting can be modulated by neural activity in excitatory nodes functionally-connected to the site of injury, and these activity-dependent processes depend on GAP-43. Critical barriers to testing this hypothesis in vivo have been the inability to serially examine global network connectivity as it evolves with recovery, and longitudinally examine subunits of remapped circuits as they change over time. We have overcome these barriers by integrating optical intrinsic signal imaging with optogenetics to probe local circuit connectivity more directly. We will use this technology to determine: 1) how the reemergence of local circuits and global networks relate to functional recovery following focal ischemia, 2) if GAP-43-dependent axonal sprouting is required for local and/or global motor network repair and behavioral recovery, and 3) if activity in excitatory motor nodes modulates local/global motor network repair and behavioral recovery, and if these changes rely on GAP-43.
项目总结/文摘

项目成果

期刊论文数量(0)
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ADAM Q BAUER其他文献

ADAM Q BAUER的其他文献

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{{ truncateString('ADAM Q BAUER', 18)}}的其他基金

Determining the efficacy of therapeutic interventions after stroke from cell specific functional connectomes
从细胞特异性功能连接组确定中风后治疗干预的功效
  • 批准号:
    10586595
  • 财政年份:
    2023
  • 资助金额:
    $ 41.89万
  • 项目类别:
Imaging and Reversibility of Cellular and Network Metabolic Dysfunction in Alzheimer's Disease
阿尔茨海默病细胞和网络代谢功能障碍的成像和可逆性
  • 批准号:
    10536491
  • 财政年份:
    2022
  • 资助金额:
    $ 41.89万
  • 项目类别:
OPTOGENETIC MAPPING OF CELL SPECIFIC CONNECTIONS IN THE MOUSE BRAIN AFTER STROKE
中风后小鼠大脑中细胞特异性连接的光遗传学图谱
  • 批准号:
    9789702
  • 财政年份:
    2018
  • 资助金额:
    $ 41.89万
  • 项目类别:
OPTOGENETIC MAPPING OF CELL SPECIFIC CONNECTIONS IN THE MOUSE BRAIN AFTER STROKE
中风后小鼠大脑中细胞特异性连接的光遗传学图谱
  • 批准号:
    10445022
  • 财政年份:
    2018
  • 资助金额:
    $ 41.89万
  • 项目类别:
OPTOGENETIC MAPPING OF CELL SPECIFIC CONNECTIONS IN THE MOUSE BRAIN AFTER STROKE
中风后小鼠大脑中细胞特异性连接的光遗传学图谱
  • 批准号:
    9661800
  • 财政年份:
    2018
  • 资助金额:
    $ 41.89万
  • 项目类别:
MECHANISMS OF FUNCTIONAL AND BEHAVIORAL RECOVERY FOLLOWING ISCHEMIC STROKE
缺血性中风后功能和行为恢复的机制
  • 批准号:
    9037714
  • 财政年份:
    2014
  • 资助金额:
    $ 41.89万
  • 项目类别:
MECHANISMS OF FUNCTIONAL AND BEHAVIORAL RECOVERY FOLLOWING ISCHEMIC STROKE
缺血性中风后功能和行为恢复的机制
  • 批准号:
    9244074
  • 财政年份:
    2014
  • 资助金额:
    $ 41.89万
  • 项目类别:
MECHANISMS OF FUNCTIONAL AND BEHAVIORAL RECOVERY FOLLOWING ISCHEMIC STROKE
缺血性中风后功能和行为恢复的机制
  • 批准号:
    8812912
  • 财政年份:
    2014
  • 资助金额:
    $ 41.89万
  • 项目类别:
MECHANISMS OF FUNCTIONAL AND BEHAVIORAL RECOVERY FOLLOWING ISCHEMIC STROKE
缺血性中风后功能和行为恢复的机制
  • 批准号:
    8700071
  • 财政年份:
    2014
  • 资助金额:
    $ 41.89万
  • 项目类别:

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