Lesion and activity dependent corticospinal tract plasticity

病变和活动依赖性皮质脊髓束可塑性

基本信息

  • 批准号:
    10413055
  • 负责人:
  • 金额:
    $ 34.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-05-19 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

Corticospinal tract (CST) injury deprives spinal circuits of movement control signals. This leads to loss of function—muscle weakness and paralysis—and gain of dysfunction—including hyperreflexia and spasticity. To repair the CST after injury and restore motor control, it is necessary to abrogate the impairments due to both the loss of function and gain of dysfunction following injury. Our research during the prior funding period shows that activity-dependent processes underlie both the loss of function and gain of dysfunction after CST injury. This finding provides the foundation for developing new therapeutic neuromodulatory approaches to target activity dependence using motor cortex (MCX) stimulation and transspinal direct current stimulation (tsDCS). MCX stimulation after injury is effective in CST repair and motor recovery. In Aim 1 we will determine the most effective MCX neuromodulation treatment to produce persistent structural and functional plasticity of the corticospinal system. Using different stimulation patterns, we will ask if efficacy depends on recruiting CST axon growth-promoting signaling. Using optogenetics to identify activated CST axons, we will test how stimulation patterns determine anatomical and physiological outcomes. Knowing that recovery is more than CST sprouting, we will ask if efficacy depends on producing long-term physiological changes in spinal circuits. We recently showed that selective CST injury or MCX inactivation produces trans-neuronal loss of spinal cholinergic interneurons and that this loss can be rescued by spinal activation. In Aim 2 we will determine how MCX neuromodulation regulates transneuronal segmental circuit remodeling after injury to promote spinal circuit repair. We will ask how CST injury impacts the major class of excitatory premotor interneurons of the CST. We will test if MCX stimulation ameliorates trans-neuronal circuit changes and then examine the interplay of repair strategies differentially targeting microglial-based spinal circuit remodeling and CST sprouting In Aim 3 we will harness the differential actions of tsDCS on spinal circuits to enhance repair and rehabilitation efficacy after cervical SCI. Spinal circuits integrate motor control signals with afferent information. After SCI, with the loss of motor pathways, spared afferent feedback dominates segmental circuit function. We recently showed that afferent competition diminishes CST connection strength, to reinforce afferent over integrated control. We will use the differential actions of tsDCS to promote spared CST function and weaken potentially “runaway” afferent input, to rebalance segmental control. We will develop a novel strategy that combines neuromodulation-based repair with neuromodulation-assisted rehabilitation to promote recovery. Successful completion of our studies will advance our understanding of the mechanisms of impairment and the mechanisms underlying novel neuromodulatory repair strategies after SCI. Results will inform how best to integrate motor behavioral rehabilitation and activity-based interventions to provide potentially clinically relevant approaches to improve motor control in humans after cervical SCI.
皮质脊髓束 (CST) 损伤会剥夺脊髓回路的运动控制信号。这会导致损失 功能——肌肉无力和麻痹——以及功能障碍的增加——包括反射亢进和痉挛。到 损伤后修复 CST 并恢复运动控制,有必要消除由于以下原因造成的损伤: 损伤后功能丧失和功能障碍增加。我们在先前资助期间的研究表明 活动依赖性过程是 CST 损伤后功能丧失和功能障碍增加的基础。这 这一发现为开发针对目标活动的新的神经调节治疗方法奠定了基础 使用运动皮层 (MCX) 刺激和经脊柱直流电刺激 (tsDCS) 的依赖性。 损伤后的 MCX 刺激对于 CST 修复和运动恢复有效。在目标 1 中,我们将确定 最有效的 MCX 神经调节治疗,可产生持久的结构和功能可塑性 皮质脊髓系统。使用不同的刺激模式,我们会询问疗效是否取决于招募 CST 轴突生长促进信号传导。使用光遗传学来识别激活的 CST 轴突,我们将测试如何 刺激模式决定解剖学和生理学结果。知道康复不仅仅是 CST 萌芽后,我们会问功效是否取决于脊髓回路产生长期的生理变化。 我们最近表明,选择性 CST 损伤或 MCX 失活会导致脊髓的跨神经元损失 胆碱能中间神经元的损失可以通过脊髓激活来挽救。在目标 2 中,我们将确定如何 MCX 神经调节调节损伤后跨神经元节段回路重塑以促进脊柱 电路维修。我们将询问 CST 损伤如何影响大脑的主要兴奋性前运动中间神经元 国家标准时间。我们将测试 MCX 刺激是否改善跨神经元回路变化,然后检查相互作用 差异化针对基于小胶质细胞的脊髓回路重塑和 CST 萌芽的修复策略 在目标 3 中,我们将利用 tsDCS 对脊髓回路的差异作用来增强修复和 颈椎SCI后的康复效果。脊髓电路将运动控制信号与传入信息集成在一起。 脊髓损伤后,随着运动通路的丧失,传入反馈主导了节段回路功能。我们 最近表明,传入竞争会削弱 CST 连接强度,从而增强传入竞争 集成控制。我们将利用 tsDCS 的差异化作用来促进幸存的 CST 功能并削弱 潜在的“失控”传入输入,以重新平衡分段控制。我们将制定一项新颖的战略 将基于神经调节的修复与神经调节辅助康复相结合以促进康复。 成功完成我们的研究将加深我们对损伤机制和 SCI 后新型神经调节修复策略的机制。结果将告诉您如何最好地 整合运动行为康复和基于活动的干预措施,以提供潜在的临床 改善颈椎 SCI 后人类运动控制的相关方法。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

John H Martin其他文献

John H Martin的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('John H Martin', 18)}}的其他基金

Interaction of Motor Learning with Transcranial Direct Current - Efficacy and Mechanisms
运动学习与经颅直流电的相互作用 - 功效和机制
  • 批准号:
    10577313
  • 财政年份:
    2022
  • 资助金额:
    $ 34.34万
  • 项目类别:
Diversity Supplement to 2R01NS064004
2R01NS064004 的多样性补充
  • 批准号:
    10303610
  • 财政年份:
    2021
  • 资助金额:
    $ 34.34万
  • 项目类别:
Combined Biomaterial and Neuromodulatory Approach to Promote Axonal Outgrowth and Connections After Cervical SCI
结合生物材料和神经调节方法促进宫颈 SCI 后轴突生长和连接
  • 批准号:
    10323048
  • 财政年份:
    2021
  • 资助金额:
    $ 34.34万
  • 项目类别:
Repairing maladaptive corticospinal tract development
修复适应不良的皮质脊髓束发育
  • 批准号:
    9256549
  • 财政年份:
    2013
  • 资助金额:
    $ 34.34万
  • 项目类别:
Repairing maladaptive corticospinal tract development
修复适应不良的皮质脊髓束发育
  • 批准号:
    8654370
  • 财政年份:
    2013
  • 资助金额:
    $ 34.34万
  • 项目类别:
Repairing maladaptive corticospinal tract development
修复适应不良的皮质脊髓束发育
  • 批准号:
    8597664
  • 财政年份:
    2013
  • 资助金额:
    $ 34.34万
  • 项目类别:
Repairing maladaptive corticospinal tract development
修复适应不良的皮质脊髓束发育
  • 批准号:
    8842211
  • 财政年份:
    2013
  • 资助金额:
    $ 34.34万
  • 项目类别:
Diversity Supplement: Lesion and Activity Dependent Corticospinal Tract Plasticity
多样性补充:病变和活动依赖性皮质脊髓束可塑性
  • 批准号:
    10431593
  • 财政年份:
    2009
  • 资助金额:
    $ 34.34万
  • 项目类别:
Lesion and activity dependent corticospinal tract plasticity
病变和活动依赖性皮质脊髓束可塑性
  • 批准号:
    7730193
  • 财政年份:
    2009
  • 资助金额:
    $ 34.34万
  • 项目类别:
Lesion and activity dependent corticospinal tract plasticity
病变和活动依赖性皮质脊髓束可塑性
  • 批准号:
    10176602
  • 财政年份:
    2009
  • 资助金额:
    $ 34.34万
  • 项目类别:

相似海外基金

Linking Epidermis and Mesophyll Signalling. Anatomy and Impact in Photosynthesis.
连接表皮和叶肉信号传导。
  • 批准号:
    EP/Z000882/1
  • 财政年份:
    2024
  • 资助金额:
    $ 34.34万
  • 项目类别:
    Fellowship
Digging Deeper with AI: Canada-UK-US Partnership for Next-generation Plant Root Anatomy Segmentation
利用人工智能进行更深入的挖掘:加拿大、英国、美国合作开发下一代植物根部解剖分割
  • 批准号:
    BB/Y513908/1
  • 财政年份:
    2024
  • 资助金额:
    $ 34.34万
  • 项目类别:
    Research Grant
Doctoral Dissertation Research: Social and ecological influences on brain anatomy
博士论文研究:社会和生态对大脑解剖学的影响
  • 批准号:
    2235348
  • 财政年份:
    2023
  • 资助金额:
    $ 34.34万
  • 项目类别:
    Standard Grant
Simultaneous development of direct-view and video laryngoscopes based on the anatomy and physiology of the newborn
根据新生儿解剖生理同步开发直视喉镜和视频喉镜
  • 批准号:
    23K11917
  • 财政年份:
    2023
  • 资助金额:
    $ 34.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Computational comparative anatomy: Translating between species in neuroscience
计算比较解剖学:神经科学中物种之间的翻译
  • 批准号:
    BB/X013227/1
  • 财政年份:
    2023
  • 资助金额:
    $ 34.34万
  • 项目类别:
    Research Grant
computational models and analysis of the retinal anatomy and potentially physiology
视网膜解剖学和潜在生理学的计算模型和分析
  • 批准号:
    2825967
  • 财政年份:
    2023
  • 资助金额:
    $ 34.34万
  • 项目类别:
    Studentship
Genetics of Extreme Phenotypes of OSA and Associated Upper Airway Anatomy
OSA 极端表型的遗传学及相关上呼吸道解剖学
  • 批准号:
    10555809
  • 财政年份:
    2023
  • 资助金额:
    $ 34.34万
  • 项目类别:
Development of a novel visualization, labeling, communication and tracking engine for human anatomy.
开发一种新颖的人体解剖学可视化、标签、通信和跟踪引擎。
  • 批准号:
    10761060
  • 财政年份:
    2023
  • 资助金额:
    $ 34.34万
  • 项目类别:
Understanding the functional anatomy of nociceptive spinal output neurons
了解伤害性脊髓输出神经元的功能解剖结构
  • 批准号:
    10751126
  • 财政年份:
    2023
  • 资助金额:
    $ 34.34万
  • 项目类别:
The Anatomy of Online Reviews: Evidence from the Steam Store
在线评论剖析:来自 Steam 商店的证据
  • 批准号:
    2872725
  • 财政年份:
    2023
  • 资助金额:
    $ 34.34万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了