▪ Abstract Motor function is severely disrupted following spinal cord injury (SCI). The spinal circuitry, however, exhibits a great degree of automaticity and plasticity after an injury. Automaticity implies that the spinal circuits have some capacity to perform complex motor tasks following the disruption of supraspinal input, and evidence for plasticity suggests that biochemical changes at the cellular level in the spinal cord can be induced in an activity-dependent manner that correlates with sensorimotor recovery. These characteristics should be strongly considered as advantageous in developing therapeutic strategies to assist in the recovery of locomotor function following SCI. Rehabilitative efforts combining locomotor training pharmacological means and/or spinal cord electrical stimulation paradigms will most likely result in more effective methods of recovery than using only one intervention.

Robotic training paradigms that enforce a fixed kinematic control might be suboptimal for rehabilitative training because they abolish variability, an intrinsic property of neuromuscular control (Jezernik et al., 2003). In the present study we introduce “assist-as-needed” (AAN) robotic training paradigms for rehabilitation of spinal cord injury subjects. To test the efficacy of these robotic control strategies to teach spinal mice to step, we divided 27 adult female Swiss–Webster mice randomly into three groups. Each group was trained robotically by using one of three control strategies: a fixed training trajectory (Fixed group), an AAN training paradigm without interlimb coordination (Band group), and an AAN training paradigm with bilateral hindlimb coordination (Window group). Beginning at 14 d after a complete midthoracic spinal cord transection, the mice were trained daily (10 min/d, 5 d/week) to step on a treadmill 10 min after the administration of quipazine (0.5 mg/kg), a serotonin agonist, for a period of 6 weeks. During weekly performance evaluations, the mice trained with the AAN window paradigm generally showed the highest level of recovery as measured by the number, consistency, and periodicity of steps during the testing sessions. In all three measurements there were no significant differences between the Band and the Fixed training groups. These results indicate that the window training approach, which includes loose alternating interlimb coordination, is more effective than a fixed trajectory paradigm with rigid alternating interlimb coordination or an AAN paradigm without any interlimb constraints in promoting robust postinjury stepping behavior.