The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats

Sławińska, Urszula; Majczyński, Henryk; Dai, Yue; Jordan, Larry M.

doi:10.1113/jphysiol.2011.224931

Cited by 78 publications

(93 citation statements)

References 48 publications

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“…We exploited this concept to design an electrochemical neuroprosthesis (3) and training procedures (4,5) that restored full weight-bearing locomotion in rats with a complete spinal cord injury (SCI). Sławińska et al, as well as many others (6,7), reported comparable observations in mice (8), rats (9), and cats (10) over the past three decades.…”

supporting

confidence: 55%

Response to Comment on “Restoring Voluntary Control of Locomotion After Paralyzing Spinal Cord Injury”

Courtine

Heutschi

Brand

2012

Science

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Sławińska et al. questioned the involvement of supraspinal centers in restoring locomotion after multisystem neuroprosthetic training in rats with paralyzing spinal cord injury. Here, we clarify misconceptions and present additional results illustrating the robust influence of brain input on electrochemically enabled spinal circuitries. We reassert that our intervention reestablished supraspinal control over hindlimb locomotion in paralyzed rats.A century ago, Sherrington reported the unexpected ability of isolated spinal circuits to generate rhythmic leg movements in response to sensory input (1). Since this seminal observation, spinal locomotion has been described in various species and conditions (2). We exploited this concept to design an electrochemical neuroprosthesis (3) and training procedures (4, 5) that restored full weight-bearing locomotion in rats with a complete spinal cord injury (SCI). Sławińska et al., as well as many others (6, 7), reported comparable observations in mice (8), rats (9), and cats (10) over the past three decades.These hindlimb movements, however, remain involuntary. In spinal animals, quadrupedal hindlimb locomotion occurs in the complete absence of supraspinal input and is controlled via sensory ensembles (5,11,12). For example, the intact forelimbs initiate locomotion and sustain propulsion during quadrupedal gait, which generates sensory feedback in the hindlimbs due to biomechanical coupling. Like the rear person in a pantomime horse, lumbosacral circuitries can recognize these task-specific sensory states and use this information to coordinate complex movements. In a recent study (11), we demonstrated that, as early as 10 days after a paralyzing SCI, quadrupedally positioned rats produced weightbearing locomotion, climbed a staircase, and steered in a curve during electrochemically enabled motor states. We did not report these results in our Science paper (13) because lumbosacral circuits control these seemingly complex quadrupedal movements without contribution from supraspinal centers. Therefore, they presented no novelty in the framework of this study. Indeed, rats with the same SCI were incapable of initiating bipedal walking [ figure 1C and movie S1 in (13)]. They also failed to sustain robotically initiated locomotion [figure S6 in (13)]. Moreover, when the robot moved nontrained rats toward a staircase, the isolated spinal circuits failed to adjust gait movements, which led to a dramatic collapse against the staircase. Together, these results demonstrate that the absence of supraspinal input led to the inability to initiate, sustain, and modulate bipedal hindlimb locomotion overground. They also reveal that quadrupedal locomotor testing yields inconclusive results and that bipedal walking is a more appropriate paradigm to uncover the ability of supraspinal centers to functionally access lumbosacral circuits.In (13), we described a type of motor control that is radically different from automated spinal stepping: that is, the recovery of supraspinal control over a rang...

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supporting

confidence: 55%

Response to Comment on “Restoring Voluntary Control of Locomotion After Paralyzing Spinal Cord Injury”

Courtine

Heutschi

Brand

2012

Science

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“…It is well established that the basic pattern of locomotion is produced by a specialized network within the spinal cord, the so-called locomotor central pattern generator (CPG) (reviewed in Frigon 2012;Kiehn 2011;McCrea and Rybak 2008). The presence of a spinal locomotor CPG working in concert with sensory feedback from the periphery allows recovery of hindlimb locomotion following complete spinal transection either spontaneously or with training in many mammalian species, such as mice (Leblond et al 2003), rats (Slawinska et al 2012), cats (Barbeau and Rossignol 1987;Lovely et al 1986), and dogs (Naito et al 1990). Spinal cord-transected (spinalized) animal models are powerful tools to assess spinal mechanisms of locomotor control and examine how sensory feedback interacts with spinal circuits during real stepping movements.…”

mentioning

confidence: 98%

The spinal control of locomotion and step-to-step variability in left-right symmetry from slow to moderate speeds

Dambreville

Labarre

Thibaudier

et al. 2015

Journal of Neurophysiology

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When speed changes during locomotion, both temporal and spatial parameters of the pattern must adjust. Moreover, at slow speeds the step-to-step pattern becomes increasingly variable. The objectives of the present study were to assess if the spinal locomotor network adjusts both temporal and spatial parameters from slow to moderate stepping speeds and to determine if it contributes to step-to-step variability in left-right symmetry observed at slow speeds. To determine the role of the spinal locomotor network, the spinal cord of 6 adult cats was transected (spinalized) at low thoracic levels and the cats were trained to recover hindlimb locomotion. Cats were implanted with electrodes to chronically record electromyography (EMG) in several hindlimb muscles. Experiments began once a stable hindlimb locomotor pattern emerged. During experiments, EMG and bilateral video recordings were made during treadmill locomotion from 0.1 to 0.4 m/s in 0.05 m/s increments. Cycle and stance durations significantly decreased with increasing speed, whereas swing duration remained unaffected. Extensor burst duration significantly decreased with increasing speed, whereas sartorius burst duration remained unchanged. Stride length, step length, and the relative distance of the paw at stance offset significantly increased with increasing speed, whereas the relative distance at stance onset and both the temporal and spatial phasing between hindlimbs were unaffected. Both temporal and spatial step-to-step left-right asymmetry decreased with increasing speed. Therefore, the spinal cord is capable of adjusting both temporal and spatial parameters during treadmill locomotion, and it is responsible, at least in part, for the step-to-step variability in left-right symmetry observed at slow speeds.

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“…The upright position itself can improve stepping. 29 Training was also accomplished with manual assistance, which may differ from robotic assist strategies and is discussed elsewhere. [30][31][32][33] Lastly, more repetition and practice facilitates training efficacy 34 ; thus, we opted for hour-long sessions.…”

mentioning

confidence: 99%

Novel Multi-System Functional Gains via Task Specific Training in Spinal Cord Injured Male Rats

Ward

Herrity

Smith

et al. 2014

Journal of Neurotrauma

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Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.

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The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats

Cited by 78 publications

References 48 publications

Response to Comment on “Restoring Voluntary Control of Locomotion After Paralyzing Spinal Cord Injury”

Response to Comment on “Restoring Voluntary Control of Locomotion After Paralyzing Spinal Cord Injury”

The spinal control of locomotion and step-to-step variability in left-right symmetry from slow to moderate speeds

Novel Multi-System Functional Gains via Task Specific Training in Spinal Cord Injured Male Rats

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