Motoneuron pool plasticity following spinal cord injury

描述（由申请人提供）：脊髓损伤后，脊髓运动神经元的特性以及汇聚于其上的兴奋性和抑制性突触通路发生改变。这种可塑性被认为是对损伤的适应性反应，弥补了下降驱动力的损失。或者，这种改变可能是适应不良的，导致肌肉痉挛和拮抗肌群在损伤后的共激活。脊髓的可塑性还提供了通过运动训练和反射调节等措施恢复功能和改善脊髓损伤后不良反应的治疗前景。在这个项目中，我们将确定运动神经元池的组织不完全脊髓损伤后的变化，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，在动物深度麻醉的同时，通过挫伤产生脊髓损伤。将未受伤的大鼠与具有不完全脊髓损伤的那些大鼠和具有不完全脊髓损伤的大鼠进行自愿运动锻炼进行比较。这些大鼠组将在以下方面进行比较：1）突触兴奋的反射源和中枢（下行和固有脊髓）源的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;以及3）由该组运动神经元支配的肌纤维的收缩特性。这些系统中的每一个的组织将根据运动神经元的固有特性和它们的放电特性来表征。将通过模拟评估由不完全脊髓损伤和损伤后运动治疗产生的变化的功能影响，使用运动神经元池-肌肉的拮抗剂对的动态模型，其参数包含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。该项目的总体目标是了解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.