Optogenetic approaches to study post-stroke recovery mechanisms

研究中风后恢复机制的光遗传学方法

基本信息

  • 批准号:
    10364739
  • 负责人:
  • 金额:
    $ 62.87万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-08-01 至 2025-11-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Stroke is the leading cause of death with very limited treatment options. This devastating neurological disease is increasingly viewed as a disease of brain connectivity as a damaged stroke area can affect both local and connected brain regions, causing disruptions in neuronal activity and metabolism network-wide. Recovery of lost function can occur after stroke and is attributed to brain remodeling in areas adjacent to or connected to the infarct. In this proposal, we aim to investigate the role of key brain circuits in post-stroke recovery at the functional, cellular and molecular level, using optogenetics, advanced live imaging and high throughput RNA sequencing techniques. Previously our lab has demonstrated that selective optogenetic neuronal stimulation in the ipsilesional motor cortex (iM1) can activate plasticity mechanisms and promote recovery. Recently we have employed the optogenetic functional MRI technique to systematically map brain-wide changes in neural circuits after stroke. We have identified key circuits altered by stroke and demonstrated two key circuits restored by iM1 stimulations. Our map data also revealed two candidate circuits that were not restored by iM1 stimulations, suggesting that greater recovery could be achieved if we can rescue these circuits by directly stimulating them. In this proposal we aim to investigate key neural circuits we identified from our activation maps and elucidate their role in post-stroke recovery. In Aim1 we will use circuit-specific optogenetic tools and functional behavior tests to interrogate the role of key circuits in post-stroke recovery. This aim will address whether these circuits have beneficial or maladaptive role during post-stroke recovery. In Aim2 we will examine cellular resolution of real-time neuronal activity dynamics in key circuits after stroke using a portable live calcium imaging system. This will elucidate the neural activity dynamics (excitatory and inhibitory) of key circuits at the cellular level, allowing us to identify the temporal profile and the key neuronal populations altered by stroke, and how iM1 stimulations affect these characteristics to enhance recovery. In Aim3 we will investigate the transcriptome of key circuit areas using RNAseq, in order to identify key molecular targets and pathways altered by stroke and by iM1 stimulations. Preliminary RNAseq analysis revealed distinct pathways altered by iM1 stimulations. We aim to perform RNAseq in multiple regions including iM1 (stimulation site) and ipsilesional thalamus (iM1- connected region) to elucidate whether similar pathways are involved, and if we can identify a common molecular signature that drive recovery. We will also perform RNAseq in both sexes in order to ascertain any sex-specific differences that may be present in post-stroke recovery. Together these results will 1) advance the understanding of neural circuit dynamics during post-stroke recovery; and 2) identify key neural circuits/cell types/molecular targets and optimal time window for designing brain stimulation strategies and other therapeutic interventions in future clinical studies.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)

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GARY K STEINBERG其他文献

GARY K STEINBERG的其他文献

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{{ truncateString('GARY K STEINBERG', 18)}}的其他基金

Investigating the pathogenesis of Moyamoya Disease using patient derived induced pluripotent stem cells
使用患者来源的诱导多能干细胞研究烟雾病的发病机制
  • 批准号:
    10487543
  • 财政年份:
    2021
  • 资助金额:
    $ 62.87万
  • 项目类别:
Investigating the pathogenesis of Moyamoya Disease using patient derived induced pluripotent stem cells
使用患者来源的诱导多能干细胞研究烟雾病的发病机制
  • 批准号:
    10373587
  • 财政年份:
    2021
  • 资助金额:
    $ 62.87万
  • 项目类别:
Stanford Neuroscience Research Cores for Gene Vectors, Microscopy, and Behaviors
斯坦福大学神经科学研究基因载体、显微镜和行为核心
  • 批准号:
    9923475
  • 财政年份:
    2019
  • 资助金额:
    $ 62.87万
  • 项目类别:
Optogenetic approaches to study post-stroke recovery mechanisms
研究中风后恢复机制的光遗传学方法
  • 批准号:
    10530685
  • 财政年份:
    2015
  • 资助金额:
    $ 62.87万
  • 项目类别:
Optogenetic approaches to study post-stroke recovery mechanisms
研究中风后恢复机制的光遗传学方法
  • 批准号:
    10211210
  • 财政年份:
    2015
  • 资助金额:
    $ 62.87万
  • 项目类别:
Optogenetic approaches to study post-stroke recovery mechanisms
研究中风后恢复机制的光遗传学方法
  • 批准号:
    9288239
  • 财政年份:
    2015
  • 资助金额:
    $ 62.87万
  • 项目类别:
Optogenetic Approaches to Functional Recovery After Stroke
中风后功能恢复的光遗传学方法
  • 批准号:
    8670793
  • 财政年份:
    2013
  • 资助金额:
    $ 62.87万
  • 项目类别:
Meningeal Mast Cells: Key effectors of stroke pathology
脑膜肥大细胞:中风病理学的关键效应器
  • 批准号:
    8512591
  • 财政年份:
    2013
  • 资助金额:
    $ 62.87万
  • 项目类别:
Optogenetic Approaches to Functional Recovery After Stroke
中风后功能恢复的光遗传学方法
  • 批准号:
    8492882
  • 财政年份:
    2013
  • 资助金额:
    $ 62.87万
  • 项目类别:
Meningeal Mast Cells: Key effectors of stroke pathology
脑膜肥大细胞:中风病理学的关键效应器
  • 批准号:
    8623155
  • 财政年份:
    2013
  • 资助金额:
    $ 62.87万
  • 项目类别:

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