USE DEPENDENT MODULATION OF SYNAPTIC PLASTICITY FOLLOWING SPINAL CORD INJURY

人类和动物都可以在脊髓完全横断损伤后恢复站立或行走的能力。执行这些任务的能力取决于特定的训练方案，说明了脊髓运动学习的重要性。猫和大鼠的胸段脊髓横断导致脊髓腰段内抑制能力的持续增加，阶梯训练使抑制能力恢复到正常水平。然而，运动神经元上的抑制性和兴奋性突触的可塑性和重组程度，运动控制中的最后共同通路，是未知的。该建议的中心假设是，完全脊髓横断导致腰屈肌和伸肌运动神经元上抑制性突触的选择性增殖，而随后的脊髓横断导致腰屈肌和伸肌运动神经元上抑制性突触的选择性增殖。 重复的踏步训练选择性地减少这些运动池内抑制性突触的数量和能力。我们将采用阶梯训练法和逆行标记技术，在电镜下对比目鱼肌和胫骨前肌运动神经元的突触学进行定量研究。我们还将使用电子显微镜免疫金技术定量研究GABA能和甘氨酸能终末与比目鱼肌和胫骨前运动神经元形成突触接触的数量和比例。这些研究将为我们理解脊髓损伤和运动训练后神经可塑性的细胞机制提供基础和关键数据。因此，拟议的研究可以在制定旨在改善脊髓损伤后运动恢复的策略方面做出重大贡献。 脊髓损伤

Both humans and animals can regain the ability to stand or step after a complete spinal cord transection injury. The ability to execute these tasks depends upon specific training regimens, illustrating the importance of motor learning in the spinal cord. A thoracic spinal cord transection in both cats and rats leads to a persistent increase in the inhibitory capacity within the lumbar portion of the spinal cord, and step training returns the inhibitory capacity towards normal levels. However, the degree of plasticity and reorganization of inhibitory and excitatory synapses upon motoneurons, the final common pathway in motor control, is not known. The central hypothesis of this proposal is that complete spinal cord transection results in a selective proliferation of inhibitory synapses upon lumbar flexor and extensor motoneurons, while subsequent repetitive step training selectively decreases the number and capacity of inhibitory synapses within these motor pools. We will use a step-training paradigm and retrograde labeling techniques to study quantitatively the synaptology of soleus and tibialis anterior motoneurons in the electron microscope. We will also use electron microscopic immunogold techniques to study quantitatively the number and ratios of GABAergic and glycinergic terminals forming synaptic contacts with soleus and tibialis anterior motoneurons. The proposed studies will provide fundamental and critical data to assist in our understanding of cellular mechanisms of neural plasticity after spinal cord injury and locomotor training. The proposed studies can therefore contribute significantly in developing strategies designed to improve motor recovery after spinal cord injury.