Changes in Motoneuron Properties and Synaptic Inputs Related to Step Training after Spinal Cord Transection in Rats

Abstract

Although recovery from spinal cord injury is generally meager, evidence suggests that step training can improve stepping performance, particularly after neonatal spinal injury. The location and nature of the changes in neural substrates underlying the behavioral improvements are not well understood. We examined the kinematics of stepping performance and cellular and synaptic electrophysiological parameters in ankle extensor motoneurons in nontrained and treadmill-trained rats, all receiving a complete spinal transection as neonates. For comparison, electrophysiological experiments included animals injured as young adults, which are far less responsive to training. Recovery of treadmill stepping was associated with significant changes in the cellular properties of motoneurons and their synaptic input from spinal white matter [ipsilateral ventrolateral funiculus (VLF)] and muscle spindle afferents. A strong correlation was found between the effectiveness of step training and the amplitude of both the action potential afterhyperpolarization and synaptic inputs to motoneurons (from peripheral nerve and VLF). These changes were absent if step training was unsuccessful, but other spinal projections, apparently inhibitory to step training, became evident. Greater plasticity of axonal projections after neonatal than after adult injury was suggested by anatomical demonstration of denser VLF projections to hindlimb motoneurons after neonatal injury. This finding confirmed electrophysiological measurements and provides a possible mechanism underlying the greater training susceptibility of animals injured as neonates. Thus, we have demonstrated an "age-at-injury"-related difference that may influence training effectiveness, that successful treadmill step training can alter electrophysiological parameters in the transected spinal cord, and that activation of different pathways may prevent functional improvement.

Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats

“…Trained rats also demonstrated increased facilitation of the ankle flexors, which could have been an effect of the repeated administration of quipazine during the training. In addition to changes in the sensorimotor pathways (Côté and Gossard, 2004), locomotor training has been shown to increase segmental and central EPSPs and decrease afterhyperpolarization depth, which lead to facilitation of motoneuron activation (Petruska et al, 2007). We showed previously that the level of ES and quipazine used in the present study does not directly induce stepping, but enables the spinal cord to respond appropriately to the proprioceptive input associated with weight bearing on a moving treadmill belt (Gerasimenko et al, 2007).…”

“…It is obvious from the marked lower number of FOSϩ nuclei in the trained than nontrained rats that aberrant spinal circuits were activated in the nontrained rats. This reorganization has been shown neurochemically, structurally, and electrophysiologically, as well as behaviorally after a complete spinal cord transection (Tillakaratne et al, 2000(Tillakaratne et al, , 2002Petruska et al, 2007). The spinal circuitry that generates stepping movements also spontaneously reorganizes after incomplete spinal cord injuries (Bareyre et al, 2004;Courtine et al, 2008).…”

Effects of antidepressant and treadmill gait training on recovery from spinal cord injury in rats

“…Furthermore, the animals injured as neonates showed greater susceptibility to training; that finding suggested that the age at injury may influence plasticity. 29 Ferreira et al 30 used short, daily training (like ours); they suggested that moderate physical exercise could modulate synaptic and structural proteins in motor brain areas, which may play an important role in exercise-dependent brain plasticity. 30 This synergistic effect had been studied previously by Engesser-Cesar et al, 11 who examined the effect of intraperitoneal fluoxetine and treadmill training on production of the hippocampal brain-derived neurotrophic factor and neurogenesis.…”

“…Exercise improved gait and led to neurological recovery, 27 probably by enabling the intrinsic neuronal circuitry. 28 The training regimen used in our study was based on a regimen previously described by Petruska et al 29 and Ferreira et al 30 Petruska et al 29 used 15-min, 6-21 cm s À1 treadmill training with SpragueDawley rats that had undergone surgical transections of the spinal cords. Those rats showed significant changes in the cellular properties of motor neurons and the synaptic input from spinal white matter and muscle spindle afferents.…”

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].…”