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Selective corticospinal tract injury in the rat induces primary afferent fiber sprouting in the spinal cord and hyperreflexia

Tan, AM;Chakrabarty, S;Kimura, H;Martin, JH;

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.