Inducing hindlimb locomotor recovery in adult rat after complete thoracic spinal cord section using repeated treadmill training with perineal stimulation only

Alluin, Olivier; Delivet-Mongrain, Hugo; Rossignol, Serge

doi:10.1152/jn.00416.2015

Cited by 41 publications

(50 citation statements)

References 56 publications

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“…Cats, rats, and mice spinalized as adults are as a rule paralyzed for some period, but if trained regularly on a treadmill, they will recover well-coordinated locomotor movements over time that can be maintained over years (6,310,392). However, directly after spinalization, adult cats can actually be made to walk on a treadmill (170), if clonidine, an ␣ 2 receptor agonist, or the noradrenergic precursor DOPA (causing a release of noradrenaline from the coeruleospinal terminals) is administered.…”

Section: A Spinal Tetrapods Can Generate Well-coordinated Locomotor mentioning

confidence: 99%

“…The chronic spinal cat is the most well-studied species with regard to recovery of locomotor function, but the same results apply also to spinal rats and mice (6). It is very important to realize this fact, since many studies of therapy for spinal cord injury have failed to take into account the ability of the spinal cord to generate locomotor movements after training.…”

Section: A Spinal Tetrapods Can Generate Well-coordinated Locomotor mentioning

confidence: 99%

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Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion

Grillner

Manira

2020

Physiological Reviews

363

395

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The vertebrate control of locomotion involves all levels of the nervous system from cortex to the spinal cord. Here, we aim to cover all main aspects of this complex behavior, from the operation of the microcircuits in the spinal cord to the systems and behavioral levels and extend from mammalian locomotion to the basic undulatory movements of lamprey and fish. The cellular basis of propulsion represents the core of the control system, and it involves the spinal central pattern generator networks (CPGs) controlling the timing of different muscles, the sensory compensation for perturbations, and the brain stem command systems controlling the level of activity of the CPGs and the speed of locomotion. The forebrain and in particular the basal ganglia are involved in determining which motor programs should be recruited at a given point of time and can both initiate and stop locomotor activity. The propulsive control system needs to be integrated with the postural control system to maintain body orientation. Moreover, the locomotor movements need to be steered so that the subject approaches the goal of the locomotor episode, or avoids colliding with elements in the environment or simply escapes at high speed. These different aspects will all be covered in the review.

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Section: A Spinal Tetrapods Can Generate Well-coordinated Locomotor mentioning

confidence: 99%

Section: A Spinal Tetrapods Can Generate Well-coordinated Locomotor mentioning

confidence: 99%

Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion

Grillner

Manira

2020

Physiological Reviews

363

395

View full text Add to dashboard Cite

show abstract

“…Mice show spontaneous recovery after transection, 53 whereas rats require training and other treatments, although locomotion can be elicited by non-invasive strategies (i.e., training and perineal stimulation). 54,55 Cats have provided important understanding of the CPG. Unlike humans, they show recovery of weight-support and locomotion after a complete spinal cord transection with single treatments such as step-training on the treadmill or delivery of neurotrophins.…”

Section: Are Animal Models Still Valuable?mentioning

confidence: 99%

Rehabilitation Strategies after Spinal Cord Injury: Inquiry into the Mechanisms of Success and Failure

Côté

Murray

Lemay

2017

Journal of Neurotrauma

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Body-weight supported locomotor training (BWST) promotes recovery of load-bearing stepping in lower mammals, but its efficacy in individuals with a spinal cord injury (SCI) is limited and highly dependent on injury severity. While animal models with complete spinal transections recover stepping with step-training, motor complete SCI individuals do not, despite similarly intensive training. In this review, we examine the significant differences between humans and animal models that may explain this discrepancy in the results obtained with BWST. We also summarize the known effects of SCI and locomotor training on the muscular, motoneuronal, interneuronal, and supraspinal systems in human and non-human models of SCI and address the potential causes for failure to translate to the clinic. The evidence points to a deficiency in neuronal activation as the mechanism of failure, rather than muscular insufficiency. While motoneuronal and interneuronal systems cannot be directly probed in humans, the changes brought upon by step-training in SCI animal models suggest a beneficial re-organization of the systems' responsiveness to descending and afferent feedback that support locomotor recovery. The literature on partial lesions in humans and animal models clearly demonstrate a greater dependency on supraspinal input to the lumbar cord in humans than in non-human mammals for locomotion. Recent results with epidural stimulation that activates the lumbar interneuronal networks and/or increases the overall excitability of the locomotor centers suggest that these centers are much more dependent on the supraspinal tonic drive in humans. Sensory feedback shapes the locomotor output in animal models but does not appear to be sufficient to drive it in humans.

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“…The presence of locomotor CPGs within the lumbar spinal cord allows for the recovery of hindlimb locomotion after spinal transection in several adult mammalian species, including mice (Leblond et al 2003), rats (Slawinska et al 2012;Alluin et al 2015) and cats (Lovely et al 1986;Barbeau & Rossignol, 1987). These chronic spinal animal models are powerful tools to investigate the control of left-right coordination during real locomotor movements by spinal mechanisms interacting with sensory feedback from the periphery.…”

Section: Introductionmentioning

confidence: 99%

Left–right coordination from simple to extreme conditions during split‐belt locomotion in the chronic spinal adult cat

Frigon

Desrochers

Thibaudier

et al. 2016

The Journal of Physiology

117

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Key pointsr Coordination between the left and right sides is essential for dynamic stability during locomotion.r The immature or neonatal mammalian spinal cord can adjust to differences in speed between the left and right sides during split-belt locomotion by taking more steps on the fast side.r We show that the adult mammalian spinal cord can also adjust its output so that the fast side can take more steps.r During split-belt locomotion, only certain parts of the cycle are modified to adjust left-right coordination, primarily those associated with swing onset.r When the fast limb takes more steps than the slow limb, strong left-right interactions persist. r Therefore, the adult mammalian spinal cord has a remarkable adaptive capacity for left-right coordination, from simple to extreme conditions. Abstract Although left-right coordination is essential for locomotion, its control is poorly understood, particularly in adult mammals. To investigate the spinal control of left-right coordination, a spinal transection was performed in six adult cats that were then trained to recover hindlimb locomotion. Spinal cats performed tied-belt locomotion from 0.1 to 1.0 m s −1 and split-belt locomotion with low to high (1:1.25-10) slow/fast speed ratios. With the left hindlimb stepping at 0.1 m s −1 and the right hindlimb stepping from 0.2 to 1.0 m s −1 , 1:1, 1:2, 1:3, 1:4 and 1:5 left-right step relationships could appear. The appearance of 1:2+ relationships was not linearly dependent on the difference in speed between the slow and fast belts. The last step taken by the fast hindlimb displayed longer cycle, stance and swing durations and increased extensor activity, as the slow limb transitioned to swing. During split-belt locomotion with 1:1, 1:2 and 1:3 relationships, the timing of stance onset of the fast limb relative to the slow limb and placement of both limbs at contact were invariant with increasing slow/fast speed ratios. In contrast, the timing of stance onset of the slow limb relative to the fast limb and the placement of both limbs at swing onset were modulated with slow/fast speed ratios. Thus, left-right coordination is adjusted by modifying specific parts of the cycle. Results highlight the remarkable adaptive capacity of the adult mammalian spinal cord, providing insight into spinal mechanisms and sensory signals regulating left-right coordination.

show abstract

Inducing hindlimb locomotor recovery in adult rat after complete thoracic spinal cord section using repeated treadmill training with perineal stimulation only

Cited by 41 publications

References 56 publications

Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion

Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion

Rehabilitation Strategies after Spinal Cord Injury: Inquiry into the Mechanisms of Success and Failure

Left–right coordination from simple to extreme conditions during split‐belt locomotion in the chronic spinal adult cat

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