Plasticity following spinalization and step-training in the cat

Locomotor training has gained in popularity and is more and more integrated in rehabilitative strategies to enhance stepping recovery in spinal cord injured (SCI) individuals. This strategy is directly inspired from several decades of work performed in the laboratory taking advantage of a spinal cat model in which reflex and locomotor pathways are exhaustively described. Completely isolated from supraspinal influences, the spinal cord has the capacity to recover stepping movements when given repetitive and appropriate sensory feedback related to step-training on a treadmill. However, the underlying mechanisms for recuperating the appropriate motor patterns are still poorly understood and are the scope of this study.; Project I. It is generally assumed that plasticity in spinal locomotor circuits is responsible for the stepping recovery. However, the repetitive sensory stimulation related to step-training could also modify transmission in reflex pathways, which are also known to contribute significantly to the level of muscle activity during stepping. In this project, transmission in reflex pathways was evaluated by measuring responses evoked by a stimulation of a cutaneous or muscle nerve of the hindpaw and recorded intracellularly in motoneurons from extensor and flexor muscles involved in ankle, knee and hip joint movements during an acute experiment in decerebrate cats. Possible modifications in reflex transmission were determined by the statistical comparison of responses between 2 groups of spinal cats (complete transection at T13), but only one was assigned to a step-training regimen. Results showed that the synaptic transmission in both group I muscle reflex pathways from extensors and cutaneous pathways were modified following one month of step-training. The monosynaptic excitation was decreased after step-training and a normal pattern of modulation was recovered during locomotion. Moreover, group Ib inhibition and polysynaptic group I excitation of extensors were respectively decreased and increased after step-training and clonidine injection, a noradrenergic agonist useful for central pattern generation. It was further observed that plasticity in cutaneous pathways was highly specific: only certain pathways were modulated (mostly depressed). Transmission of cutaneous input originating from the sole of the foot was particularly modified. Overall, step-training is suggested to both decrease the hyperexcitability observed in reflex pathways after SCI and to facilitate the recruitment of antigravity muscles to assist recovery and weight-bearing.; Project II. There is now strong evidence that spinal circuits can be affected by activity-dependent biochemical processes that influence its ability to recover, perform and maintain an adequate locomotor pattern. Investigations have recently been oriented toward molecules involved in LTP to determine if similar mechanisms are both implicated in hippocampal learning and spinal motor learning. Given the preponderant effect of ERK on synaptic plasticity and function and its role in integrating signals from the cell surface to transcription factors, ERK appears to be a potential candidate for mediating the beneficial effects of step-training and may participate in the synaptic events associated with locomotor recovery after SCI. Protein expression was compared between 3 groups of cats (intact, SCI, SCI and step-trained) using western blot analysis of homogenates of spinal cord segments. The study focussed on assessing relative levels of ERK and pERK proteins. Results showed that ERK activation is up-regulated in a majority of lumbar segments following SCI and is specifically down-regulated in L5 by step-training. These results suggest that ERK activation is involved in long-term plasticity following SCI and that it may be detrimental to locomotor generation, at least in specific spinal segments.; Keywords. cutaneous reflex pathways, CPG, CREB, ERK, intracellular recording, locomotio...