Spinal control of muscle synergies for adult mammalian locomotion.

KEY POINTS: The control of locomotion is thought to be generated by activating groups of muscles that perform similar actions, which are termed muscle synergies. Here, we investigated if muscle synergies are controlled at the level of the spinal cord. We did this by comparing muscle activity in the legs of cats during stepping on a treadmill before and after a complete spinal transection that abolishes commands from the brain. We show that muscle synergies were maintained following spinal transection, validating the concept that muscle synergies for locomotion are primarily controlled by circuits of neurons within the spinal cord. ABSTRACT: Locomotion is thought to involve the sequential activation of functional modules or muscle synergies. Here, we tested the hypothesis that muscle synergies for locomotion are organized within the spinal cord. We recorded bursts of muscle activity in the same cats (n = 7) before and after spinal transection during tied-belt locomotion at three speeds and split-belt locomotion at three left-right speed differences. We identified seven muscles synergies before (intact state) and after (spinal state) spinal transection. The muscles comprising the different synergies were the same in the intact and spinal states as well as at different speeds or left-right speed differences. However, there were some significant shifts in the onsets and offsets of certain synergies as a function of state, speed and left-right speed differences. The most notable difference between the intact and spinal states was a change in the timing between the knee flexor and hip flexor muscle synergies. In the intact state, the knee flexor synergy preceded the hip flexor synergy, whereas in the spinal state both synergies occurred concurrently. Afferent inputs also appear important for the expression of some muscle synergies, specifically those involving biphasic patterns of muscle activity. We propose that muscle synergies for locomotion are primarily organized within the spinal cord, although their full expression and proper timing requires inputs from supraspinal structures and/or limb afferents.

A Spinal Mechanism Related to Left-Right Symmetry Reduces Cutaneous Reflex Modulation Independently of Speed During Split-Belt Locomotion.

Task- and phase-dependent reflex modulation during locomotion is well established, but we do not know the signals driving this modulation. To determine whether signals related to left-right symmetry of the locomotor pattern modulate cutaneous reflexes, we stimulated the superficial peroneal nerve in five intact female cats and in four spinal-transected cats (spinal cats, two males and two females) during split-belt locomotion at different left-right speeds. We compared cutaneous reflexes evoked in three ipsilateral and two contralateral hindlimb muscles during split-belt locomotion with those evoked during tied-belt (equal left-right speeds) locomotion at matched speeds of the slow and fast limbs. Our results showed similar phase-dependent modulation of cutaneous reflexes during tied-belt and split-belt locomotion in intact and spinal cats. During tied-belt locomotion in intact cats, an increase in speed significantly increased reflex modulation from minimum to maximum values, whereas in spinal cats, we observed a significant decrease. However, in all muscles of intact and spinal cats, split-belt locomotion significantly reduced reflex modulation compared with tied-belt locomotion independently of which limb was stepping on the slow or fast belt. Additionally, reflex modulation correlated more with spatial left-right symmetry, as opposed to a temporal one, in intact and spinal cats. Our results indicate that signals related to left-right symmetry reduce cutaneous reflex modulation independently of speed via a spinal mechanism. We propose that asymmetric sensory feedback from the left and right legs alters the state of the spinal network, thereby reducing cutaneous reflexes to prevent inputs from destabilizing a potentially unstable pattern.SIGNIFICANCE STATEMENT When we contact an obstacle during walking, receptors in the skin send signals to the CNS to alter the trajectory of the leg to maintain balance. This response, or reflex, is different when the leg is in the air and when it is contacting the ground. The reflex also differs when we walk at different speeds. Here, we investigated this reflex when the left and right legs were walking at different speeds on a split-belt treadmill in cats. We show that the reflex is smaller during split-belt locomotion compared with when both legs are walking at equal speeds. We propose that the spinal locomotor network controlling walking reduces the reflex response to optimize balance when gait is unstable.

The modulation of locomotor speed is maintained following partial denervation of ankle extensors in spinal cats.

Speed modulation requires spatiotemporal adjustments and altered neural drive to different muscles. The loss of certain muscles produces changes in the locomotor pattern and functional compensation. However, how the loss of specific muscles affects speed modulation has not been specifically investigated. Here, we denervated the lateral gastrocnemius and soleus muscles unilaterally in seven cats that had recovered hindlimb locomotion following complete spinal transection (spinal cats). Hindlimb locomotion was tested at 10 speeds, from 0.1 to 1.0 m/s, before, 1-2 days, and 1-8 wk after denervation. Six of seven cats performed hindlimb locomotion 1-2 days postdenervation at all speeds, with the exception of two out of those six cats that did not perform stable stepping at 0.9 and 1.0 m/s. All seven cats performed hindlimb locomotion 1-8 wk postdenervation at all speeds. In some cats, at 1-2 days postdenervation, the ipsilateral hindlimb performed more steps than the contralateral hindlimb, particularly at slow speeds. This 2:1 coordination disappeared over time. In three cats, the linear increase in the amplitude of the electromyography of the ipsilateral medial gastrocnemius was reduced with increasing speed early after denervation before recovering later on. Overall, the results indicate that spinal circuits interacting with sensory feedback from the hindlimbs compensate for the partial loss of ankle extensors, retaining the ability to modulate locomotor speed. NEW & NOTEWORTHY We investigated speed modulation after denervating 2 ankle extensors unilaterally at 10 treadmill speeds in spinal-transected cats. Although we observed new forms of left-right coordination and changes in muscle activity of a remaining synergist, modulation of spatiotemporal variables with increasing speed was largely maintained after denervation. The results indicate that spinal locomotor centers interacting with sensory feedback compensate for the loss of ankle extensors, allowing speed modulation.

Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat.

When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response.SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the contacted limb and opposite homologous limb help maintain balance and forward progression. Here, we investigated reflexes during quadrupedal locomotion in the cat by electrically stimulating cutaneous nerves in each of the four limbs. Functionally, responses appear to modify the trajectory or stabilize the movement of the stimulated limb while modifying the support phase of the other limbs. Reflexes between limbs are mediated by fast-conducting pathways that involve excitatory and inhibitory circuits controlling each limb. The comparatively stronger descending pathways from cervical to lumbar circuits controlling the forelimbs and hindlimbs, respectively, could serve a protective function.

Lack of adaptation during prolonged split-belt locomotion in the intact and spinal cat.

KEY POINTS: During split-belt locomotion in humans where one leg steps faster than the other, the symmetry of step lengths and double support periods of the slow and fast legs is gradually restored. When returning to tied-belt locomotion, there is an after-effect, with a reversal in the asymmetry observed in the early split-belt period, indicating that the new pattern was stored within the central nervous system. In this study, we investigated if intact and spinal-transected cats show a similar pattern of adaptation to split-belt locomotion by measuring kinematic variables and electromyography before, during and after 10 min of split-belt locomotion. The results show that cats do not adapt to prolonged split-belt locomotion. Our results suggest an important physiological difference in how cats and humans respond to prolonged asymmetric locomotion. ABSTRACT: In humans, gait adapts to prolonged walking on a split-belt treadmill, where one leg steps faster than the other, by gradually restoring the symmetry of interlimb kinematic variables, such as double support periods and step lengths, and by reducing muscle activity (EMG, electromyography). The adaptation is also characterized by reversing the asymmetry of interlimb variables observed during the early split-belt period when returning to tied-belt locomotion, termed an after-effect. To determine if cats adapt to prolonged split-belt locomotion and to assess if spinal locomotor circuits participate in the adaptation, we measured interlimb variables and EMG in intact and spinal-transected cats before, during and after 10 min of split-belt locomotion. In spinal cats, only the hindlimbs performed stepping with the forelimbs stationary. In intact and spinal cats, step lengths and double support periods were, on average, symmetric, during tied-belt locomotion. They became asymmetric during split-belt locomotion and remained asymmetric throughout the split-belt period. Upon returning to tied-belt locomotion, symmetry was immediately restored. In intact cats, the mean EMG amplitude of hindlimb extensors increased during split-belt locomotion and remained increased throughout the split-belt period, whereas in spinal cats, EMG amplitude did not change. Therefore, the results indicate that the locomotor pattern of cats does not adapt to prolonged split-belt locomotion, suggesting an important physiological difference in the control of locomotion between cats and humans. We propose that restoring left-right symmetry is not required to maintain balance during prolonged asymmetric locomotion in the cat, a quadruped, as opposed to human bipedal locomotion.

Reflex wind-up in early chronic spinal injury: plasticity of motor outputs.

In this study we evaluate temporal summation (wind-up) of reflexes in select distal and proximal hindlimb muscles in response to repeated stimuli of the distal tibial or superficial peroneal nerves in cats 1 mo after complete spinal transection. This report is a continuation of our previous paper on reflex wind-up in the intact and acutely spinalized cat. To evaluate reflex wind-up in both studies, we recorded electromyographic signals from the following left hindlimb muscles: lateral gastrocnemius (LG), tibialis anterior (TA), semitendinosus (ST), and sartorius (Srt), in response to 10 electrical pulses to the tibial or superficial peroneal nerves. Two distinct components of the reflex responses were considered, a short-latency compound action potential (CAP) and a longer duration bout of sustained activity (SA). These two response types were shown to be differentially modified by acute spinal injury in our previous work (Frigon A, Johnson MD, Heckman CJ. J Physiol 590: 973-989, 2012). We show that these responses exhibit continued plasticity during the 1-mo recovery period following acute spinalization. During this early chronic phase, wind-up of SA responses returned to preinjury levels in one muscle, the ST, but remained depressed in all other muscles tested. In contrast, CAP response amplitudes, which were initially potentiated following acute transection, returned to preinjury levels in all muscles except for Srt, which continued to show marked increase. These findings illustrate that spinal elements exhibit considerable plasticity during the recovery process following spinal injury and highlight the importance of considering SA and CAP responses as distinct phenomena with unique underlying neural mechanisms.NEW & NOTEWORTHY This research is the first to assess temporal summation, also called wind-up, of muscle reflexes during the 1-mo recovery period following spinal injury. Our results show that two types of muscle reflex activity are differentially modulated 1 mo after spinal cord injury (SCI) and that spinal reflexes are altered in a muscle-specific manner during this critical period. This postinjury plasticity likely plays an important role in spasticity experienced by individuals with SCI.

Nonlinear Modulation of Cutaneous Reflexes with Increasing Speed of Locomotion in Spinal Cats.

Cutaneous reflexes are important for responding rapidly to perturbations, correcting limb trajectory, and strengthening support. During locomotion, they are modulated by phase to generate functionally appropriate responses. The goal of the present study was to determine whether cutaneous reflexes and their phase-dependent modulation are altered with increasing speed and if this is accomplished at the spinal level. Four adult cats that recovered stable hindlimb locomotion after spinal transection were implanted with electrodes to record hindlimb muscle activity chronically and to stimulate the superficial peroneal nerve electrically to evoke cutaneous reflexes. The speed-dependent modulation of cutaneous reflexes was assessed by evoking and characterizing ipsilateral and contralateral responses in semitendinosus, vastus lateralis, and lateral gastrocnemius muscles at four treadmill speeds: 0.2, 0.4, 0.6, and 0.8 m/s. The amplitudes of ipsilateral and contralateral responses were largest at intermediate speeds of 0.4 and 0.6 m/s, followed by the slowest and fastest speeds of 0.2 and 0.8 m/s, respectively. The phase-dependent modulation of reflexes was maintained across speeds, with ipsilateral and contralateral responses peaking during the stance-to-swing transition and swing phase of the ipsilateral limb or midstance of the contralateral limb. Reflex modulation across speeds also correlated with the spatial symmetry of the locomotor pattern, but not with temporal symmetry. That the cutaneous reflex amplitude in all muscles was similarly modulated with increasing speed independently of the background level of muscle activity is consistent with a generalized premotoneuronal spinal control mechanism that could help to stabilize the locomotor pattern when changing speed.SIGNIFICANCE STATEMENT When walking, receptors located in the skin respond to mechanical pressure and send signals to the CNS to correct the trajectory of the limb and to reinforce weight support. These signals produce different responses, or reflexes, if they occur when the foot is contacting the ground or in the air. This is known as phase-dependent modulation of reflexes. However, when walking at faster speeds, we do not know if and how these reflexes are changed. In the present study, we show that reflexes from the skin are modulated with speed and that this is controlled at the level of the spinal cord. This modulation could be important in preventing sensory signals from destabilizing the walking pattern.

Interlimb Coordination during Tied-Belt and Transverse Split-Belt Locomotion before and after an Incomplete Spinal Cord Injury.

Coordination between the arms/forelimbs and legs/hindlimbs is often impaired in humans and quadrupedal mammals after incomplete spinal cord injury. In quadrupeds, the forelimbs often take more steps than the hindlimbs, producing a two-to-one forelimb-hindlimb (2-1 FL-HL) coordination. In locomotor performance scales, this is generally considered a loss of FL-HL coordination. Here, FL-HL coordination was quantified before and 8 weeks after a lateral spinal hemisection at the sixth thoracic segment in six adult cats. Cats were tested during tied-belt locomotion (equal front and rear speeds) and transverse split-belt locomotion with the forelimbs or hindlimbs stepping faster. The results show that consistent phasing between forelimb and hindlimb movements was maintained after hemisection, even with the appearance of 2-1 FL-HL coordination, indicating that new stable forms of coordination emerge. Moreover, transverse split-belt locomotion potently modulated interlimb coordination and was capable of restoring a one-to-one FL-HL coordination with a faster treadmill speed for the hindlimbs. In conclusion, the results suggest that neural communication persists after an incomplete spinal cord injury, despite an unequal number of steps between the forelimbs and hindlimbs, and that interlimb coordination can be modulated by having the forelimbs or hindlimbs move at a faster frequency. We propose that locomotor recovery scales incorporate more sensitive methods to quantify FL-HL coordination, to better reflect residual functional capacity and possible cervicolumbar neural communication. Lastly, devising training protocols that make use of the bidirectional influences of the cervical and lumbar locomotor pattern generators could strengthen interlimb coordination and promote locomotor recovery.

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

KEY POINTS: Coordination between the left and right sides is essential for dynamic stability during locomotion. 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. We show that the adult mammalian spinal cord can also adjust its output so that the fast side can take more steps. During split-belt locomotion, only certain parts of the cycle are modified to adjust left-right coordination, primarily those associated with swing onset. When the fast limb takes more steps than the slow limb, strong left-right interactions persist. 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.

Adaptive muscle plasticity of a remaining agonist following denervation of its close synergists in a model of complete spinal cord injury.

Complete spinal cord injury (SCI) alters the contractile properties of skeletal muscle, and although exercise can induce positive changes, it is unclear whether the remaining motor system can produce adaptive muscle plasticity in response to a subsequent peripheral nerve injury. To address this, the nerve supplying the lateral gastrocnemius (LG) and soleus muscles was sectioned unilaterally in four cats that had recovered hindlimb locomotion after spinal transection. In these spinal cats, kinematics and electromyography (EMG) were collected before and for 8 wk after denervation. Muscle histology was performed on LG and medial gastrocnemius (MG) bilaterally in four spinal and four intact cats. In spinal cats, cycle duration for the hindlimb ipsilateral or contralateral to the denervation could be significantly increased or decreased compared with predenervation values. Stance duration was generally increased and decreased for the contralateral and ipsilateral hindlimbs, respectively. The EMG amplitude of MG was significantly increased bilaterally after denervation and remained elevated 8 wk after denervation. In spinal cats the ipsilateral LG was significantly smaller than the contralateral LG, whereas the ipsilateral MG weighed significantly more than the contralateral MG. Histological characterizations revealed significantly larger fiber areas for type IIa fibers of the ipsilateral MG in three of four spinal cats. Microvascular density in the ipsilateral MG was significantly higher than in the contralateral MG. In intact cats, no differences were found for muscle weight, fiber area, or microvascular density between homologous muscles. Therefore, the remaining motor system after complete SCI retains the ability to produce adaptive muscle plasticity.

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

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.

Effect of stimulating the lumbar skin caudal to a complete spinal cord injury on hindlimb locomotion.

Sensory feedback is a potent modulator of the locomotor pattern generated by spinal networks. The purpose of this study was to assess the effect of cutaneous inputs from the back on the spinal-generated locomotor pattern. The spinal cord of six adult cats was transected at low thoracic levels. Cats were then trained to recover hindlimb locomotion. During experiments, the skin overlying lumbar vertebrae L2 to L7 was mechanically stimulated by a small calibrated clip or by manual pinching. Trials without and with cutaneous stimulation were performed at a treadmill speed of 0.4 m/s. Although manually pinching the skin completely stopped hindlimb locomotion and abolished weight support, cutaneous stimulation with the calibrated clip produced smaller effects. Specifically, more focalized cutaneous stimulation with the clip reduced flexor and extensor muscle activity and led to a more caudal positioning of the paw at contact and liftoff. Moreover, cutaneous stimulation with the clip led to a greater number of steps with improper nonplantigrade paw placements at contact and paw drag at the stance-to-swing transition. The most consistent effects on the hindlimb locomotor pattern were observed with cutaneous stimulation at midlumbar levels, from L3 to L5. The results indicate that cutaneous stimulation of the skin modulates the excitability of spinal circuits involved in generating locomotion and weight support, particularly at spinal segments thought to be critical for rhythm generation.

Modulation of phase durations, phase variations, and temporal coordination of the four limbs during quadrupedal split-belt locomotion in intact adult cats.

Stepping along curvilinear paths produces speed differences between the inner and outer limb(s). This can be reproduced experimentally by independently controlling left and right speeds with split-belt locomotion. Here we provide additional details on the pattern of the four limbs during quadrupedal split-belt locomotion in intact cats. Six cats performed tied-belt locomotion (same speed bilaterally) and split-belt locomotion where one side (constant side) stepped at constant treadmill speed while the other side (varying side) stepped at several speeds. Cycle, stance, and swing durations changed in parallel in homolateral limbs with shorter and longer stance and swing durations on the fast side, respectively, compared with the slow side. Phase variations were quantified in all four limbs by measuring the slopes of the regressions between stance and cycle durations (rSTA) and between swing and cycle durations (rSW). For a given limb, rSTA and rSW were not significantly different from one another on the constant side whereas on the varying side rSTA increased relative to tied-belt locomotion while rSW became more negative. Phase variations were similar for homolateral limbs. Increasing left-right speed differences produced a large increase in homolateral double support on the slow side, while triple-support periods decreased. Increasing left-right speed differences altered homologous coupling, homolateral coupling on the fast side, and coupling between the fast hindlimb and slow forelimb. Results indicate that homolateral limbs share similar control strategies, only certain features of the interlimb pattern adjust, and spinal locomotor networks of the left and right sides are organized symmetrically.

Speed-dependent modulation of phase variations on a step-by-step basis and its impact on the consistency of interlimb coordination during quadrupedal locomotion in intact adult cats.

It is well established that stance duration changes more than swing duration for a given change in cycle duration. Small variations in cycle duration are also observed at any given speed on a step-by-step basis. To evaluate the step-by-step effect of speed on phase variations, we measured the slopes of the linear regressions between the phases (i.e., stance, swing) and cycle duration during individual episodes at different treadmill speeds in five adult cats. We also determined the pattern of dominance, defined as the phase that varies most with cycle duration. We found a significant effect of speed on hindlimb phase variations, with significant differences observed between the slowest speed of 0.3 m/s compared with faster speeds. Moreover, although patterns of phase dominance were primarily stance/extensor dominated at the slowest speeds, as speed increased the patterns were increasingly categorized as covarying, whereby both stance/extensor and swing/flexor phases changed in approximately equal proportion with cycle duration. Speed significantly affected the relative duration of support periods as well as interlimb phasing between homolateral and diagonal pairs of limbs but not between homologous pairs of limbs. Speed also significantly affected the consistency of interlimb coordination on a step-by-step basis, being less consistent at the slowest speed of 0.3 m/s compared with faster speeds. We found a strong linear relationship between hindlimb phase variations and the consistency of interlimb coordination. Therefore, results show that phase variations on a step-by-step basis are modulated by speed, which appears to influence the consistency of interlimb coordination.

Split-belt walking alters the relationship between locomotor phases and cycle duration across speeds in intact and chronic spinalized adult cats.

During overground or treadmill walking, the stance phase and cycle durations are reduced as speed increases, whereas swing phase duration remains relatively invariant. When the speed of the left and right sides is unequal, as is the case during split-belt locomotion or when walking along a circular path, adjustments in stance and swing phases are observed, which could alter the phase/cycle duration relationships. Here, we tested this hypothesis in the left and right hindlimbs of four intact and two chronic spinal-transected adult cats during tied-belt (i.e., equal left and right speeds) and split-belt (i.e., unequal left and right speeds) walking. During split-belt walking, one side (i.e., constant limb) walked at a constant speed while the other side (varying limb) varied its speed from 0.3 to 1.0 m/s. We show that the phase/cycle duration relationships differed in both hindlimbs concurrently during split-belt walking. Specifically, the slope of the phase/cycle duration relationships for the stance/extension phase increased in the varying limb from tied-belt to split-belt walking, whereas that of the swing/flexion phase decreased. In contrast, in the constant limb, the slope of the phase/cycle duration relationships for the stance/extension phase decreased, whereas that of the swing/flexion phase increased. The results were qualitatively similar in intact and spinal-transected cats, indicating that the modulation was mediated within the spinal cord. In conclusion, we propose that neuronal networks within the spinal cord that control left and right hindlimb locomotion can differentially and simultaneously modulate phase variations when the two sides walk at different speeds.

Synchronous and asynchronous electrically evoked motor activities during wind-up stimulation are differentially modulated following an acute spinal transection.

In this study, we used a novel technique to study reflex wind-up when the spinal cord is intact and following an acute spinal transection. Specifically, we evaluated reflex responses evoked by a series of 10 electrical pulses to the tibial or superficial peroneal nerves in 9 decerebrate adult cats, before and after an acute spinal transection. Electromyograms were recorded in four hindlimb muscles (lateral gastrocnemius, tibialis anterior, semitendinosus, and sartorius) to evaluate reflex amplitude, duration, and the temporal summation of reflex responses, so-called wind-up. We identified two distinct reflex responses evoked by electrical stimulation of the tibial or superficial peroneal nerves on the basis of their pattern of change following acute spinal transection, a short-latency (∼10 ms) compound action potential (CAP) that was followed by a burst of sustained activity (SA). Wind-up of CAP and SA amplitudes was clearly present when the spinal cord was intact but was drastically reduced after acute spinalization in some muscles. Moreover, CAP and SA reflex responses were differentially modified by the acute spinalization. When the effects of acute spinal transection were significant, CAP responses were increased after acute spinalization, whereas SA responses were reduced, suggesting that the two signals are regulated by different neuronal mechanisms. The present results provide the first assessment of reflex wind-up before and after an acute spinal transection in the same animals and indicate that different reflex components must be considered separately when evaluating changes in neuronal excitability following SCI.

Sensory regulation of quadrupedal locomotion: a top-down or bottom-up control system?

Propriospinal pathways are thought to be critical for quadrupedal coordination by coupling cervical and lumbar central pattern generators (CPGs). However, the mechanisms involved in relaying information between girdles remain largely unexplored. Using an in vitro spinal cord preparation in neonatal rats, Juvin and colleagues (Juvin et al. 2012) have recently shown sensory inputs from the hindlimbs have greater influence on forelimb CPGs than forelimb sensory inputs on hindlimb CPGs, in other words, a bottom-up control system. However, results from decerebrate cats suggest a top-down control system. It may be that both bottom-up and top-down control systems exist and that the dominance of one over the other is task or context dependent. As such, the role of sensory inputs in controlling quadrupedal coordination before and after injury requires further investigation.

Cutaneous inputs from the back abolish locomotor-like activity and reduce spastic-like activity in the adult cat following complete spinal cord injury.

Spasticity is a condition that can include increased muscle tone, clonus, spasms, and hyperreflexia. In this study, we report the effect of manually stimulating the dorsal lumbosacral skin on spontaneous locomotor-like activity and on a variety of reflex responses in 5 decerebrate chronic spinal cats treated with clonidine. Cats were spinalized 1 month before the terminal experiment. Stretch reflexes were evoked by stretching the left triceps surae muscles. Crossed reflexes were elicited by electrically stimulating the right tibial or superficial peroneal nerves. Wind-up of reflex responses was evoked by electrically stimulating the left tibial or superficial peroneal nerves. We found that pinching the skin of the back abolished spontaneous locomotor-like activity. We also found that back pinch abolished the rhythmic activity observed during reflex testing without eliminating the reflex responses. Some of the rhythmic episodes of activity observed during reflex testing were consistent with clonus with an oscillation frequency greater than 3 Hz. Pinching the skin of the back effectively abolished rhythmic activity occurring spontaneously or evoked during reflex testing, irrespective of oscillation frequency. The results are consistent with the hypothesis that locomotion and clonus are produced by common central pattern-generators. Stimulating the skin of the back could prove helpful in managing undesired rhythmic activity in spinal cord-injured humans.