SPINAL MECHANISMS CONTROLLING MOTONEURON EXCITABILITY

控制运动神经元兴奋性的脊髓机制

• 批准号: 2416368
• 负责人: FLOYD J. THOMPSON
• 金额: $ 11.55万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2416368
• 关键词: GABA receptor; disease /disorder model; laboratory rat; membrane potentials; motor neurons; neural inhibition; neural plasticity; spastic paralysis; spinal cord injury; spinal reflex

DESCRIPTION (Taken from applicant's abstract) These investigators have recently observed a robust change in rate-depression (a progressive decline in the monosynaptic reflex at low stimulation frequencies) in rats following the type of spinal cord injury which typically induces spasticity in humans. This experimental model provides an opportunity to determine some essential features of the neurosubstrate and cellular mechanisms of rate-depression. Preliminary data show that rate-depression is significantly reduced by blockade of GABAb receptors by intrathecal administration of a specific GABAb antagonist. However, both spinal and supraspinal sites could have accounted for these observations. Experiments in Specific Aim 1 are proposed using intraspinal microinjection of GABAb agonists and antagonists to identify specific sites within the spinal cord which alter rate-depression. These studies will more specifically define the segmental neural substrate and cellular mechanisms of action of rate-depression. Further evidence indicates that rate- depression can be significantly influenced by microstimulation of cell clusters in the brainstem which are associated with the densest spinal projection of serotonergic fibers. Therefore, insights into the descending control of rate-depression will be sought using microstimulation to identify brainstem neuron and fiber clusters which significantly alter the expression of rate-depression. These studies will increase understanding of the descending control of reflex excitability as well as account for changes which occur following spinal cord injury. Experiments in Specific Aim 2 will determine how specific changes in reflex excitability may correlate to the experimental manifestation of spastic hyperreflexia. These experiments will correlate the time course and magnitude of alterations in the dynamic stretch reflexes of lower leg calf muscles to specific changes in spinal reflex excitability following midthoracic spinal hemisection. In addition the specific role of GABAb receptors in the maintenance of normal muscle tone, as well as the development and persistence of spastic hypertonia of calf muscle dynamic stretch reflexes will be determined. In summary, the proposed experiments will increase our understanding of the mechanism and organization of a fundamental process which regulates motoneuron excitability and how changes in the mechanism may contribute to the development of spastic hypertonia.

描述（摘自申请人摘要） 这些研究者 我最近观察到一个强大的变化率抑郁症（一个渐进的 在低刺激频率下的单突触反射下降）， 脊髓损伤后的大鼠， 人类的痉挛 该实验模型提供了一个 有机会确定一些基本特征的 神经底物和细胞机制的速率抑制。 初步 数据显示， 通过鞘内施用特异性的GABAb受体阻断剂， GABAb拮抗剂。 然而，脊柱和脊柱上部位都可以 解释了这些观察结果。 特定目标实验 1建议使用椎管内微量注射GABAb激动剂 和拮抗剂来识别脊髓内的特定位点 从而改变心率降低。 这些研究将更具体地 定义节段性神经基质和细胞机制， 速率抑制作用。 进一步的证据表明，利率- 微刺激可以显著影响抑郁症， 脑干中的细胞簇， 肾上腺素能纤维的脊髓投射。 因此， 速率抑制的下降控制将使用 微刺激以识别脑干神经元和纤维簇， 显著改变心率抑制的表达。 这些 研究将增加对下降控制的理解， 反射兴奋性，以及帐户的变化， 脊髓损伤后。 《特定目标2》中的实验将 确定反射兴奋性的具体变化如何与 痉挛性反射亢进的实验表现 这些 实验将把变化的时间进程和幅度联系起来， 小腿肌肉的动态拉伸反射， 脊髓反射兴奋性的特定变化 胸中部脊髓半切术 此外，具体作用 GABAb受体在维持正常肌张力，以及 小腿肌肉痉挛性张力亢进的发生和持续 将测定动态牵张反射。 总而言之， 建议的实验将增加我们对该机制的理解 以及调节运动神经元的基本过程的组织 兴奋性和机制的变化如何可能有助于 痉挛性肌张力亢进的发展