Department of Physiology, Pharmacology, and Neuroscience, The City College of the City University of New York, New York, New York 10031, USA.
J Neurosci. 2012 Sep 12;32(37):12896-908. doi: 10.1523/JNEUROSCI.6451-11.2012.
The corticospinal tract (CST) has dense contralateral and sparse ipsilateral spinal cord projections that converge with proprioceptive afferents on common spinal targets. Previous studies in adult rats indicate that the loss of dense contralateral spinal CST connections after unilateral pyramidal tract section (PTx), which models CST loss after stroke or spinal cord injury, leads to outgrowth from the spared side into the affected, ipsilateral, spinal cord. The reaction of proprioceptive afferents after this CST injury, however, is not known. Knowledge of proprioceptive afferent responses after loss of the CST could inform mechanisms of maladaptive plasticity in spinal sensorimotor circuits after injury. Here, we hypothesize that the loss of the contralateral CST results in a reactive increase in muscle afferents from the impaired limb and enhancement of their physiological actions within the cervical spinal cord. We found that 10 d after PTx, proprioceptive afferents sprout into cervical gray matter regions denervated by the loss of CST terminations. Furthermore, VGlut1-positive boutons, indicative of group 1A afferent terminals, increased on motoneurons. PTx also produced an increase in microglial density within the gray matter regions where CST terminations were lost. These anatomical changes were paralleled by reduction in frequency-dependent depression of the H-reflex, suggesting hyperreflexia. Our data demonstrate for the first time that selective CST injury induces maladaptive afferent fiber plasticity remote from the lesion. Our findings suggest a novel structural reaction of proprioceptive afferents to the loss of CST terminations and provide insight into mechanisms underlying spasticity.
皮质脊髓束(CST)在对侧有密集的投射,而在同侧有稀疏的投射,这些投射与本体感觉传入纤维在共同的脊髓靶点汇聚。先前的成年大鼠研究表明,单侧锥体束切断(PTx)后密集的对侧 CST 连接的丧失,模拟了中风或脊髓损伤后 CST 的丧失,导致来自对侧未受损侧的生长进入受影响的同侧脊髓。然而,这种 CST 损伤后本体感觉传入的反应尚不清楚。了解 CST 丧失后本体感觉传入的反应可以为损伤后脊髓感觉运动回路的适应性可塑性机制提供信息。在这里,我们假设 CST 的丧失导致受损肢体的肌梭传入纤维反应性增加,并增强其在颈脊髓内的生理作用。我们发现,在 PTx 后 10 天,本体感觉传入纤维在 CST 终止丧失的颈灰质区域中发芽。此外,VGlut1 阳性终扣,提示 I 类传入纤维终扣,在运动神经元上增加。PTx 还导致 CST 终止丧失的灰质区域内小胶质细胞密度增加。这些解剖学变化与 H 反射的频率依赖性抑制减少相平行,提示反射亢进。我们的数据首次证明,选择性 CST 损伤会导致远离病变的传入纤维可塑性适应不良。我们的发现表明本体感觉传入纤维对 CST 终止丧失的一种新的结构反应,并为痉挛的机制提供了深入的了解。