Motoneuron pool plasticity following spinal cord injury

描述(申请人提供)：脊髓损伤后，脊髓运动神经元的特性以及汇聚在脊髓运动神经元上的兴奋性和抑制性突触通路发生变化。这种可塑性被认为是对损伤的一种适应性反应，以补偿下行动力的丧失。或者，这种改变可能是不适应的，导致损伤后肌肉痉挛和拮抗肌群的共同激活。脊髓的可塑性也为通过运动训练和反射调节等措施恢复脊髓损伤后的功能和减轻不良反应提供了治疗的希望。在这个项目中，我们将确定脊髓不完全性损伤后运动神经元池组织的变化，运动训练对这些变化的影响，以及这些变化对运动神经元池功能的影响。这些研究将使用不完全脊髓损伤的大鼠模型进行，在该模型中，脊髓损伤是在动物深度麻醉的情况下由挫伤造成的。未受伤的大鼠将与不完全脊髓损伤的大鼠进行比较，并与给予自愿运动锻炼的不完全脊髓损伤的大鼠进行比较。这些组大鼠将从以下方面进行比较：1)反射源和中枢(下行和固有的)突触兴奋源在运动神经元池中的强度和分布；2)突触抑制的反射源的强度和分布；3)由这组运动神经元支配的肌纤维的收缩特性。每个系统的组织将根据运动神经元的固有属性和它们的放电特征来表征。不完全脊髓损伤和损伤后运动疗法所产生的变化对功能的影响将通过模拟使用一对运动神经元池-肌肉的动力学模型来评估，该模型的参数包含了在这些研究中观察到的突触、运动神经元池和肌肉组织的变化。本项目的总体目标是了解一种常见类型的脊髓损伤对运动神经元池及其控制的肌肉的组织和功能的影响，并评估运动训练的益处和局限性。

DESCRIPTION (provided by applicant): Following spinal cord injury, alterations occur in the properties of spinal motoneurons and in the excitatory and inhibitory synaptic pathways that converge upon them. This plasticity has been considered an adaptive response to injury, compensating for loss of descending drive. Alternatively, such alterations may be maladaptive, contributing to muscle spasticity and coactivation of antagonist muscle groups following injury. The plasticity of the spinal cord also offers the promise of therapies to restore function and ameliorate adverse effects following spinal cord injury through such measures as locomotor training and reflex conditioning. In this project we will identify changes in the organization of motoneuron pools following incomplete spinal cord injuries, the effect of locomotor training on these changes, and the impact of these changes on motoneuron pool function. These studies will be conducted using a rat model of incomplete spinal cord injury in which a spinal cord injury is produced by contusion while the animal is deeply anesthetized. Uninjured rats will be compared to those with incomplete spinal cord injury and to rats with incomplete spinal cord injury given access to voluntary locomotor exercise. These groups of rats will be compared with respect to 1) the strength and distribution in a motoneuron pool of a reflex source and a central (descending and propriospinal) source of synaptic excitation; 2) the strength and distribution of a reflex source of synaptic inhibition; and 3) the contractile properties of muscle fibers innervated by this group of motoneurons. The organization of each of these systems will be characterized according to the intrinsic properties of the motoneurons and their discharge characteristics. The functional impact of changes produced by incomplete spinal cord injury and by exercise therapy following injury will be assessed by simulation, using a dynamic model of an antagonist pair of motoneuron pool-muscles whose parameters incorporate the changes in synaptic, motoneuron pool and muscle organization observed in these studies. The overall goal of this project is to gain an understanding of the effects of a common type of spinal cord injury on the organization and function of a motoneuron pool and the muscle it controls and to assess the benefits and limitations locomotor training.