Chronic inactivation of the contralesional hindlimb motor cortex after thoracic spinal cord hemisection impedes locomotor recovery in the rat.

After incomplete spinal cord injury (SCI), cortical plasticity is involved in hindlimb locomotor recovery. Nevertheless, whether cortical activity is required for motor map plasticity and recovery remains unresolved. Here, we combined a unilateral thoracic spinal cord injury (SCI) with a cortical inactivation protocol that uncovered a functional role of contralesional cortical activity in hindlimb recovery and ipsilesional map plasticity. In adult rats, left hindlimb paralysis was induced by sectioning half of the spinal cord at the thoracic level (hemisection) and we used a continuous infusion of muscimol (GABAA agonist, 10 mM, 0.11 µl/h) delivered via implanted osmotic pump (n = 9) to chronically inactivate the contralesional hindlimb motor cortex. Hemisected rats with saline infusion served as a SCI control group (n = 8), and intact rats with muscimol infusion served as an inactivation control group (n = 6). Locomotion was assessed in an open field, on a horizontal ladder, and on a treadmill prior to and for three weeks after hemisection. Cortical inactivation after hemisection significantly impeded hindlimb locomotor recovery in all tasks and specifically disrupted the ability of rats to generate proper flexion of the affected hindlimb during stepping compared to SCI controls, with no significant effect of inactivation in intact rats. Chronic and acute (n = 4) cortical inactivation after hemisection also significantly reduced the representation of the affected hindlimb in the ipsilesional motor cortex derived with intracortical microsimulation (ICMS). Our results provide evidence that residual activity in the contralesional hindlimb motor cortex after thoracic hemisection contributes to spontaneous locomotor recovery and map plasticity.