Mechanisms of Reciprocal Inhibition Development

相互抑制发展的机制

基本信息

  • 批准号:
    8914046
  • 负责人:
  • 金额:
    $ 31.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-01 至 2017-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Sensory feedback regarding limb position is critical for normal locomotion and adaptation to external perturbations during movement. Feedback relating to rapid changes in muscle stretch, conveyed to the spinal cord by proprioceptive Ia sensory afferents, is especially important in this regard. While Ia afferents make some monosynaptic connections with motor neurons (MNs), direct proprioceptive influence on MN activity is exceptional; in general, proprioceptive feedback to MNs is indirect via interneuronal circuits of the spinal cord. These circuits integrate sensory feedback with centrally generated patterns of activity to modulate MN responses. Despite the importance of these more complex circuits in shaping motor output, very little is known about how these circuits are formed. Developmental mechanisms that control the establishment of proprioceptive input to interneuronal circuits, even those containing a single interneuron class, are virtually unknown. One simple sensory-motor circuit is responsible for reciprocal inhibition (RI), which acts to prevent co- contraction of antagonist flexor and extensor muscles at a joint. This sensory-motor circuit contains a single class of interneuron, the glycinergic Ia inhibitory interneuron (IaIN). These interneurons receive sensory information about muscle stretch through monosynaptic inputs from Ia afferents supplying specific muscles. Normal development of RI requires assembly of multiple, modular circuits responding to activation of Ia afferents arising from specific muscles and inhibiting functionally appropriate MN targets. What developmental mechanisms guide this process? Activity-induced RI circuit modulation in early postnatal animals suggests the possibility that activity-dependent mechanisms may be involved in the establishment of Ia sensory afferent connections with functionally appropriate subsets of IaINs. Experiments presented in this proposal will directly test this hypothesis by investigating the status of afferent connectivity with RI circuits at the initial stages of its development. We will test the necessity and sufficiency of proprioceptive afferent activity in the process of afferent segregation onto subsets of IaINs using genetic strategies in mice. Development of reciprocal inhibition mediated by IaINs is fundamental to the development of normal locomotion, and reduced RI is associated with abnormal voluntary movement and locomotion. Understanding the progression and mechanisms of normal RI development will provide an important context and perspective for understanding the expression of abnormal motor behaviors in disease and injury states.
描述(由申请人提供):关于肢体位置的感觉反馈对于运动期间的正常运动和适应外部扰动至关重要。在这方面,与通过本体感受Ia感觉传入传递到脊髓的肌肉拉伸的快速变化相关的反馈尤其重要。虽然Ia传入与运动神经元(MN)进行一些单突触连接,但对MN活动的直接本体感受影响是例外的;一般而言,对MN的本体感受反馈是通过脊髓的神经元间回路间接的。这些回路将感觉反馈与中枢产生的活动模式相结合,以调节MN反应。尽管这些更复杂的电路在形成电机输出方面很重要,但人们对这些电路是如何形成的知之甚少。控制本体感受输入到中间神经元回路的建立的发育机制,即使是包含单个中间神经元类别的那些,实际上是未知的。 一个简单的感觉-运动回路负责相互抑制(RI),其用于防止关节处的拮抗屈肌和伸肌的共同收缩。这种感觉-运动回路包含单一类别的中间神经元,即甘氨酸能Ia抑制性中间神经元(IaIN)。这些中间神经元通过供应特定肌肉的Ia传入神经的单突触输入接收关于肌肉拉伸的感觉信息。 RI的正常发展需要组装多个模块化回路,这些回路响应于来自特定肌肉的Ia传入的激活并抑制功能上适当的MN靶点。什么样的发展机制指导这一进程?活动诱导的RI电路调制在出生后早期的动物表明,活动依赖性机制可能参与建立Ia感觉传入连接与功能适当的IaINs的子集。在这个建议中提出的实验将直接测试这一假设,通过调查的状态传入连接RI电路在其发展的初始阶段。我们将测试的必要性和充分性的本体感受传入活动的过程中的传入隔离到亚群的IaIN使用遗传策略在小鼠中。 由IaINs介导的相互抑制的发展是正常运动发展的基础,RI降低与异常自主运动和运动有关。了解正常RI发展的进展和机制将为理解疾病和损伤状态下异常运动行为的表达提供重要的背景和视角。

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Calcium homeostasis in parvalbumin DRG neurons is altered after sciatic nerve crush and sciatic nerve transection injuries.
坐骨神经挤压和坐骨神经横断损伤后,小白蛋白 DRG 神经元的钙稳态发生改变。
  • DOI:
    10.1152/jn.00707.2020
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Walters,MarieC;Ladle,DavidR
  • 通讯作者:
    Ladle,DavidR
Analysis of Proprioceptive Sensory Innervation of the Mouse Soleus: A Whole-Mount Muscle Approach.
小鼠比目鱼的本体感受感官神经的分析:一种整体肌肉方法。
  • DOI:
    10.1371/journal.pone.0170751
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Sonner MJ;Walters MC;Ladle DR
  • 通讯作者:
    Ladle DR
Early postnatal development of GABAergic presynaptic inhibition of Ia proprioceptive afferent connections in mouse spinal cord.
小鼠脊髓中 Ia 本体感觉传入连接的 GABA 能突触前抑制的出生后早期发育。
  • DOI:
    10.1152/jn.00783.2012
  • 发表时间:
    2013
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Sonner,PatrickM;Ladle,DavidR
  • 通讯作者:
    Ladle,DavidR
Facilitation of antagonist motor output through short-latency sensory pathways during postnatal development in the mouse.
在小鼠出生后发育过程中通过短潜伏期感觉通路促进拮抗运动输出。
  • DOI:
    10.1016/j.neulet.2018.03.015
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Sonner,PatrickM;Ladle,DavidR
  • 通讯作者:
    Ladle,DavidR
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David R. Ladle其他文献

David R. Ladle的其他文献

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{{ truncateString('David R. Ladle', 18)}}的其他基金

Mechanisms of Reciprocal Inhibition Development
相互抑制发展的机制
  • 批准号:
    8323489
  • 财政年份:
    2011
  • 资助金额:
    $ 31.94万
  • 项目类别:
Mechanisms of Reciprocal Inhibition Development
相互抑制发展的机制
  • 批准号:
    8238568
  • 财政年份:
    2011
  • 资助金额:
    $ 31.94万
  • 项目类别:
Mechanisms of Reciprocal Inhibition Development
相互抑制发展的机制
  • 批准号:
    8536965
  • 财政年份:
    2011
  • 资助金额:
    $ 31.94万
  • 项目类别:

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