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（取自申请人的摘要）这些调查人员 最近观察到率抑郁症发生了牢固的变化（渐进性 低刺激频率下单突触反射的下降） 大鼠遵循通常诱发的脊髓损伤类型 人类的痉挛。 这个实验模型提供了 确定一些基本特征的机会 率抑制的神经基底和细胞机制。 初步的 数据表明，比率抑郁大大降低了 通过鞘内给药特异性的封锁GABAB受体 GABAB拮抗剂。 但是，脊柱和脊柱上部位都可以 已经考虑了这些观察。 特定目的的实验 使用Gabab激动剂的脊柱内显微注射提出1 和拮抗剂以识别脊髓内的特定位点 改变率抑郁症。 这些研究将更具体地 定义节段神经底物和细胞机制 费率抑郁的作用。 进一步的证据表明 - 抑郁症可能会受到微刺激的显着影响 脑干中的细胞簇与最密集相关 血清素能纤维的脊柱投影。 因此，洞察力 将寻求对费率抑郁的下降控制 微刺激以鉴定脑干神经元和纤维簇，这些神经元和纤维簇 显着改变率抑郁的表达。 这些 研究将增加对对降级控制的理解 反射兴奋性以及考虑发生的变化 脊髓损伤后。 特定目标2中的实验将 确定反射兴奋性的特定变化如何相关 痉挛性超反射症的实验表现。 这些 实验将使时间过程和变化的幅度相关联 在下腿小腿肌肉的动态拉伸反射中 脊柱反射兴奋性的特定变化以下 胸腔半脊髓半分裂。 此外， 维持正常肌肉张力的GABAB受体以及 小腿肌肉痉挛性高血压的发育和持久性 将确定动态拉伸反射。 总而言之， 建议的实验将增加我们对机制的理解 以及组织的基本过程，该过程调节运动神经元 兴奋性以及机制的变化可能有助于 痉挛性高渗的发展。