Sparing of Descending Axons Rescues Interneuron Plasticity in the Lumbar Cord to Allow Adaptive Learning After Thoracic Spinal Cord Injury.
Sparing of Descending Axons Rescues Interneuron Plasticity in the Lumbar Cord to Allow Adaptive Learning After Thoracic Spinal Cord Injury.
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DOI：
10.3389/fncir.2016.00011
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发表时间：
2016
影响因子：
3.5
通讯作者：
Basso DM
中科院分区：
文献类型：
--
作者：
Hansen CN;Faw TD;White S;Buford JA;Grau JW;Basso DM
本研究评估了在胸椎脊髓损伤（SCI）后腰椎扩大中，保留轴突在结构和行为神经可塑性中的作用。先前的研究表明，在不完全损伤后，保留轴突的恢复增加了随后完全性脊髓横断（TX）后的行为输出。这表明，未受影响的轴突直接影响腰椎下层神经元网络的适应性变化。我们假设腰椎神经元网络通过防止异常可塑性来支持行为增益。因此，本研究测量了完全性TX或完全性挫伤（SCI）后孤立腰椎的组织学和功能变化。为了测量腰椎的功能可塑性，我们使用了一种已建立的工具学习范式（ILP）。在这种情况下，孤立腰椎节段内的神经回路通过增加屈曲持续时间来减少暴露于有害腿部休克的学习。我们采用该模型，采用原理验证设计来评估在啮齿动物模型中胸段脊髓损伤后早期（7天）或后期（42天）保留对腰椎学习和可塑性的作用。脊髓损伤或TX后7天早期，无论动物是否有轴突底物恢复，脊髓学习都无法实现。在负责感觉运动整合和学习的中间神经元群体中，学习失败伴随着细胞体细胞萎缩和异常树突棘表达的测量而发生。另一种方法是，将腰椎暴露于少量未受损伤的轴突6周后，脊髓损伤后期的学习能力接近正常。与此同时，中间神经元的胞体体积增大，异常树突棘减少。因此，影响运动网络中基于活动的学习的机会取决于保留的轴突限制适应性不良的可塑性。总之，这项工作确定了运动网络中备用轴突系统和适应性可塑性之间的时间依赖性相互作用，并强调了基于活动的康复的关键窗口。
This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI). Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX). This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI). To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm (ILP). In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days) or late (42 days) after midthoracic SCI in a rodent model. Early after SCI or TX at 7 days, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between spared axonal systems and adaptive plasticity in locomotor networks and highlights a critical window for activity-based rehabilitation.