Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats

Abstract

Locomotor training improves function after a spinal cord injury both in experimental and clinical settings. The activity-dependent mechanisms underlying such improvement, however, are sparsely understood. Adult rats received a complete spinal cord transection (T9), and epidural stimulation (ES) electrodes were secured to the dura matter at L2. EMG electrodes were implanted bilaterally in selected muscles. Using a servo-controlled body weight support system for bipedal stepping, five rats were trained 7 d/week for 6 weeks (30 min/d) under quipazine (0.3 mg/kg) and ES (L2; 40 Hz). Nontrained rats were handled as trained rats but did not receive quipazine or ES. At the end of the experiment, a subset of rats was used for c-fos immunohistochemistry. Three trained and three nontrained rats stepped for 1 h (ES; no quipazine) and were returned to their cages for 1 h before intracardiac perfusion. All rats could step with ES and quipazine administration. The trained rats had higher and longer steps, narrower base of support at stance, and lower variability in EMG parameters than nontrained rats, and these properties approached that of noninjured controls. After 1 h of stepping, the number of FOSϩ neurons was significantly lower in trained than nontrained rats throughout the extent of the lumbosacral segments. These results suggest that training reinforces the efficacy of specific sensorimotor pathways, resulting in a more selective and stable network of neurons that controls locomotion.

Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury

“…The present findings in rats and humans demonstrate that recovery after severe SCI will also necessitate directing and exploiting compensatory plasticity to preserve and improve the functional capacities of denervated spinal sensorimotor circuits (Dietz, 2010). Electrochemically-enabled training is capable of promoting useful remodelling of spinal circuits and functional improvement in severely paralysed rats (Ichiyama et al, 2008(Ichiyama et al, , 2011Courtine et al, 2009;. Robotically assisted training also shows efficacy to improve both spinal reflex behaviour and mobility in individuals with incomplete SCI (Hubli et al, 2012).…”

“…Rats were returned to their cages and perfused exactly 60 min after stepping (Ichiyama et al, 2008;Courtine et al, 2009). All animals were deeply anaesthetized by an intraperitoneal injection of 0.5 ml pentobarbital-Na (50 mg/ml) and transcardially perfused with $80 ml Ringer's solution containing 100 000 IU/l heparin (Liquemin, Roche) and 0.25% NaNO 2 followed by 300 ml of cold 4% phosphate buffered paraformaldehyde, pH 7.4 containing 5% sucrose.…”

“…To address this question, we studied the expression pattern of the activity-dependent early gene protein c-fos in response to a continuous bout of electrochemically-enabled stepping (Ichiyama et al, 2008;Courtine et al, 2009). Rats in the chronic stage of SCI exhibited a 2-fold increase in the number of c-fos on neurons in motor-related spinal regions (laminae 7 to 10) compared with intact rats (P 5 0.001; Fig.…”

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

“…A battery of behavioral tests has been developed in the past decades to study movement function after SCi. Kinematic analysis gives detailed information about locomotor control, and software tools are available to quantify limb movements [42,43] .…”

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

“…More recent studies using cervical lesion models, with the functional emphasis on fine motor control of hand/paw function, confirmed these ideas and related plasticity at various levels of the CNS to the recovery of motor function. Not surprisingly, the mechanisms read like a list found under spontaneous plasticity including the up-regulation of growth/plasticity associated factors ( [43]; reviewed in Krajacic et al [35] and Vaynman et al [44]) and sprouting of lesioned fibers [45], as well as changes in spinal circuitries [17,38,39,[46][47][48], cortical maps [35,45], and in neuronal properties [49,50].…”