Locomotor Training Maintains Normal Inhibitory Influence on Both Alpha- and Gamma-Motoneurons after Neonatal Spinal Cord Transection

Abstract

Spinal cord injuries lead to impairments, which are accompanied by extensive reorganization of neuronal circuits caudal to the injury. Locomotor training can aid in the functional recovery after injury, but the neuronal mechanisms associated with such plasticity are only sparsely known. We investigated ultrastructurally the synaptic inputs to tibialis anterior motoneurons (MNs) retrogradely labeled in adult rats that had received a complete midthoracic spinal cord transection at postnatal day 5. A subset of the injured rats received locomotor training. Both ␥-and ␣-MNs were studied. The total number of boutons apposing ␥-MNs, but not ␣-MNs, was reduced after neonatal spinal cord transection. The proportion of inhibitory to excitatory boutons, however, was increased significantly in both ␣-MNs and ␥-MNs in spinally transected rats, but with locomotor training returned to levels observed in intact rats. The specific densities and compositions of synaptic boutons were, however, different between all three groups. Surprisingly, we observed the atypical presence of both C-and M-type boutons apposing the somata of ␥-MNs in the spinal rats, regardless of training status. We conclude that a neonatal spinal cord transection induces significant reorganization of synaptic inputs to spinal motoneurons caudal to the site of injury with a net increase in inhibitory influence, which is associated with poor stepping. Spinal cord injury followed by successful locomotor training, however, results in improved bipedal stepping and further synaptic changes with the proportion of inhibitory and excitatory inputs to the motoneurons being similar to that observed in intact rats.

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

“…Undirected plasticity of denervated circuits leads to the development of neuronal dysfunction in the chronic stage of injury Previous investigations in animal models of SCI documented the progressive upregulation of receptor, synapse and fibre density in spinal circuitries deprived of supraspinal input (Krenz and Weaver, 1998;Kitzman, 2006;Boulenguez et al, 2010;Ichiyama et al, 2011;Kapitza et al, 2012;Tan et al, 2012;Bos et al, 2013). In the present study, we also found a multiplicity of plastic changes in spinal segments caudal to a staggered lateral hemisection SCI.…”

“…Although previous studies reported contrasting and variable conclusions, they consistently highlighted the progressive upregulation of receptor (Murray et al, 2010), synapse (Kitzman, 2006;Ichiyama et al, 2011;Kapitza et al, 2012;Tan et al, 2012), and fibre density (Krenz and Weaver, 1998;Ballermann and Fouad, 2006;Hou et al, 2008Hou et al, , 2009) in response to the interruption of supraspinal input. Likewise, ablation of afferent pathways in the brain provokes the formation of new fibre arborizations and spines in the affected region (Kirov and Harris, 1999).…”

“…Various studies in experimental animals uncovered a mosaic of injury-induced molecular and cellular changes in segments caudal to a SCI (Krenz and Weaver, 1998;Ballermann and Fouad, 2006;Kitzman, 2006Kitzman, , 2007Soares et al, 2007;Hou et al, 2008;Tan et al, 2008;Hou et al, 2009;Boulenguez et al, 2010;Murray et al, 2010;Ichiyama et al, 2011;Singh et al, 2011;Kapitza et al, 2012;Tan et al, 2012). Depending upon the SCI model and specific functional assessments, these alterations in the properties of neuronal circuits have alternatively been classified as beneficial or detrimental.…”

The effect of timing electrical stimulation to robotic-assisted stepping on neuromuscular activity and associated kinematics

“…There is also evidence that treadmill training restored a normal balance of excitatory to inhibitory synapses, thereby improving motor neuron activity [45]. Results from this study, as well as the literature, indicate that FES alone can have some benefit in improving locomotor capability, such as improved step length and improved spinal reflexes.…”

“…The ability to modulate spinal plasticity, and resulting functional recovery, by hind-limb afferent stimuli has also been demonstrated in a number of previous studies [41][42][43]. Recent evidence that FES of cutaneous afferent pathways is effective in modulating the generation of stepping in cats and humans with SCI [44][45] could indicate that applied stimulation may enhance afferent modulation of spinal circuitry.…”