SPINAL MECHANISMS CONTROLLING MOTONEURON EXCITABILITY

控制运动神经元兴奋性的脊髓机制

• 批准号: 2272083
• 负责人: FLOYD J. THOMPSON
• 金额: $ 11.61万
• 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/2272083
• 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(摘自申请人的摘要)这些调查人员 最近观察到了比率抑郁(渐进性)的强劲变化 在低刺激频率下单突触反射的下降) 大鼠遵循脊髓损伤的类型，这种损伤通常导致 人类的痉挛。此实验模型提供了一种 有机会确定的一些基本特征 心率抑制的神经底物和细胞机制。初步 数据显示，速度抑制显著减少了 鞘内给药阻断GABAB受体的研究 GABAB拮抗剂。然而，脊柱和脊柱上的部位都可能 解释了这些观察结果。有针对性的实验 1拟采用椎管内微量注射GABAB激动剂 和拮抗剂来识别脊髓内的特定位置 这会改变失调率。这些研究将更具体地 明确节段性神经底物和细胞机制 降压率作用。进一步的证据表明- 微刺激可显著影响抑郁。 脑干中的细胞团，与密度最高的 5-羟色胺能纤维的脊髓投射。因此，对 将使用以下方法寻求速率抑制的下降控制 微刺激以识别脑干神经元和纤维簇 显著改变率抑制的表达。这些 研究将增加对下行控制的理解 反映兴奋性，并解释发生的变化 在脊髓损伤之后。在特定目标2中的实验将 确定反射兴奋性的具体变化可能如何相互关联 痉挛反射亢进的实验表现。这些 实验将把变化的时间进程和大小联系起来 在小腿小腿肌肉的动态伸展反射中 术后脊髓反射兴奋性的特殊变化 中胸段脊柱半横切。此外，它的具体作用是 GABAB受体在维持正常肌张力中的作用 小腿肌肉痉挛性高张症的发生和持续 将确定动态伸展反射。总而言之， 拟议的实验将增加我们对这一机制的理解 以及管理运动神经元的基本过程的组织 兴奋性以及机制的变化可能如何有助于 痉挛性高张力症的发展。