Changes in intra- and interlimb reflexes from forelimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

In quadrupeds, such as cats, cutaneous afferents from the forepaw dorsum signal external perturbations and send signals to spinal circuits to coordinate the activity in muscles of all four limbs. How these cutaneous reflex pathways from forelimb afferents are reorganized after an incomplete spinal cord injury is not clear. Using a staggered thoracic lateral hemisections paradigm, we investigated changes in intralimb and interlimb reflex pathways by electrically stimulating the left and right superficial radial nerves in seven adult cats and recording reflex responses in five forelimb and ten hindlimb muscles. After the first (right T5-T6) and second (left T10-T11) hemisections, forelimb-hindlimb coordination was altered and weakened. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-, mid- and long-latency homonymous and crossed reflex responses in forelimb muscles and their phase modulation remained largely unaffected after staggered hemisections. The occurrence of homolateral and diagonal mid- and long-latency responses in hindlimb muscles evoked with left and right superficial radial nerve stimulation was significantly reduced at the first time point after the first hemisection, but partially recovered at the second time point with left superficial radial nerve stimulation. These responses were lost or reduced after the second hemisection. When present, all reflex responses, including homolateral and diagonal, maintained their phase-dependent modulation. Therefore, our results show a considerable loss in cutaneous reflex transmission from cervical to lumbar levels after incomplete spinal cord injury, albeit with preservation of phase modulation, likely affecting functional responses to external perturbations.

Forelimb movements contribute to hindlimb cutaneous reflexes during locomotion in cats.

During quadrupedal locomotion, interactions between spinal and supraspinal circuits and somatosensory feedback coordinate forelimb and hindlimb movements. How this is achieved is not clear. To determine whether forelimb movements modulate hindlimb cutaneous reflexes involved in responding to an external perturbation, we stimulated the superficial peroneal nerve in six intact cats during quadrupedal locomotion and during hindlimb-only locomotion (with forelimbs standing on stationary platform) and in two cats with a low spinal transection (T12-T13) during hindlimb-only locomotion. We compared cutaneous reflexes evoked in six ipsilateral and four contralateral hindlimb muscles. Results showed similar occurrence and phase-dependent modulation of short-latency inhibitory and excitatory responses during quadrupedal and hindlimb-only locomotion in intact cats. However, the depth of modulation was reduced in the ipsilateral semitendinosus during hindlimb-only locomotion. Additionally, longer-latency responses occurred less frequently in extensor muscles bilaterally during hindlimb-only locomotion, whereas short-latency inhibitory and longer-latency excitatory responses occurred more frequently in the ipsilateral and contralateral sartorius anterior, respectively. After spinal transection, short-latency inhibitory and excitatory responses were similar to both intact conditions, whereas mid- or longer-latency excitatory responses were reduced or abolished. Our results in intact cats and the comparison with spinal-transected cats suggest that the absence of forelimb movements suppresses inputs from supraspinal structures and/or cervical cord that normally contribute to longer-latency reflex responses in hindlimb extensor muscles.NEW & NOTEWORTHY During quadrupedal locomotion, the coordination of forelimb and hindlimb movements involves central circuits and somatosensory feedback. To demonstrate how forelimb movement affects hindlimb cutaneous reflexes during locomotion, we stimulated the superficial peroneal nerve in intact cats during quadrupedal and hindlimb-only locomotion as well as in spinal-transected cats during hindlimb-only locomotion. We show that forelimb movement influences the modulation of hindlimb cutaneous reflexes, particularly the occurrence of long-latency reflex responses.

Operation regimes of spinal circuits controlling locomotion and role of supraspinal drives and sensory feedback.

Locomotion in mammals is directly controlled by the spinal neuronal network, operating under the control of supraspinal signals and somatosensory feedback that interact with each other. However, the functional architecture of the spinal locomotor network, its operation regimes, and the role of supraspinal and sensory feedback in different locomotor behaviors, including at different speeds, remain unclear. We developed a computational model of spinal locomotor circuits receiving supraspinal drives and limb sensory feedback that could reproduce multiple experimental data obtained in intact and spinal-transected cats during tied-belt and split-belt treadmill locomotion. We provide evidence that the spinal locomotor network operates in different regimes depending on locomotor speed. In an intact system, at slow speeds (< 0.4 m/s), the spinal network operates in a non-oscillating state-machine regime and requires sensory feedback or external inputs for phase transitions. Removing sensory feedback related to limb extension prevents locomotor oscillations at slow speeds. With increasing speed and supraspinal drives, the spinal network switches to a flexor-driven oscillatory regime and then to a classical half-center regime. Following spinal transection, the spinal network can only operate in the state-machine regime. Our results suggest that the spinal network operates in different regimes for slow exploratory and fast escape locomotor behaviors, making use of different control mechanisms.

Changes in intra- and interlimb reflexes from hindlimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in the four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked cutaneous reflexes by electrically stimulating left and right superficial peroneal nerves before and after two thoracic lateral hemisections placed on opposite sides of the cord at 9- to 13-week interval in seven adult cats (4 males and 3 females). We recorded reflex responses in ten hindlimb and five forelimb muscles bilaterally. After the first (right T5-T6) and second (left T10-T11) hemisections, coordination of the fore- and hindlimbs was altered and/or became less consistent. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-latency reflex responses in homonymous and crossed hindlimb muscles largely remained unaffected after staggered hemisections. However, mid- and long-latency homonymous and crossed responses in both hindlimbs occurred less frequently after staggered hemisections. In forelimb muscles, homolateral and diagonal mid- and long-latency response occurrence significantly decreased after the first and second hemisections. In all four limbs, however, when present, short-, mid- and long-latency responses maintained their phase-dependent modulation. We also observed reduced durations of short-latency inhibitory homonymous responses in left hindlimb extensors early after the first hemisection and delayed short-latency responses in the right ipsilesional hindlimb after the first hemisection. Therefore, changes in cutaneous reflex responses correlated with impaired balance/stability and interlimb coordination during locomotion after spinal cord injury. Restoring reflex transmission could be used as a biomarker to facilitate locomotor recovery. KEY POINTS: Cutaneous afferent inputs coordinate muscle activity in the four limbs during locomotion when the foot dorsum contacts an obstacle. Thoracic spinal cord injury disrupts communication between spinal locomotor centres located at cervical and lumbar levels, impairing balance and limb coordination. We investigated cutaneous reflexes during quadrupedal locomotion by electrically stimulating the superficial peroneal nerve bilaterally, before and after staggered lateral thoracic hemisections of the spinal cord in cats. We showed a loss/reduction of mid- and long-latency responses in all four limbs after staggered hemisections, which correlated with altered coordination of the fore- and hindlimbs and impaired balance. Targeting cutaneous reflex pathways projecting to the four limbs could help develop therapeutic approaches aimed at restoring transmission in ascending and descending spinal pathways.

Simultaneous control of forward and backward locomotion by spinal sensorimotor circuits.

Mammals walk in different directions, such as forward and backward. In human infants/adults and decerebrate cats, one leg can walk forward and the other backward simultaneously on a split-belt treadmill, termed hybrid or bidirectional locomotion. The purpose of the present study was to determine if spinal sensorimotor circuits generate hybrid locomotion and if so, how the limbs remain coordinated. We tested hybrid locomotion in 11 intact cats and in five following complete spinal thoracic transection (spinal cats) at three treadmill speeds with the hindlimbs moving forward, backward or bidirectionally. All intact cats generated hybrid locomotion with the forelimbs on a stationary platform. Four of five spinal cats generated hybrid locomotion, also with the forelimbs on a stationary platform, but required perineal stimulation. During hybrid locomotion, intact and spinal cats positioned their forward and backward moving hindlimbs caudal and rostral to the hip, respectively. The hindlimbs maintained consistent left-right out-of-phase alternation in the different stepping directions. Our results suggest that spinal locomotor networks generate hybrid locomotion by following certain rules at phase transitions. We also found that stance duration determined cycle duration in the different locomotor directions/conditions, consistent with a common rhythm-generating mechanism for different locomotor directions. Our findings provide additional insight on how left-right spinal networks and sensory feedback from the limbs interact to coordinate the hindlimbs and provide stability during locomotion in different directions. KEY POINTS: Terrestrial mammals can walk forward and backward, which is controlled in part by spinal sensorimotor circuits. Humans and cats also perform bidirectional or hybrid locomotion on a split-belt treadmill with one leg going forward and the other going backward. We show that cats with a spinal transection can perform hybrid locomotion and maintain left-right out-of-phase coordination, indicating that spinal sensorimotor circuits can perform simultaneous forward and backward locomotion. We also show that the regulation of cycle duration and phase duration is conserved across stepping direction, consistent with a common rhythm-generating mechanism for different stepping directions. The results help us better understand how spinal networks controlling the left and right legs enable locomotion in different directions.

Neuromechanical Strategies for Obstacle Negotiation during Overground Locomotion following Incomplete Spinal Cord Injury in Adult Cats.

Following incomplete spinal cord injury in animals, including humans, substantial locomotor recovery can occur. However, functional aspects of locomotion, such as negotiating obstacles, remains challenging. We collected kinematic and electromyography data in 10 adult cats (5 males, 5 females) before and at weeks 1-2 and 7-8 after a lateral mid-thoracic hemisection on the right side of the cord while they negotiated obstacles of three different heights. Intact cats always cleared obstacles without contact. At weeks 1-2 after hemisection, the ipsilesional right hindlimb contacted obstacles in ∼50% of trials, triggering a stumbling corrective reaction or absent responses, which we termed Other. When complete clearance occurred, we observed exaggerated ipsilesional hindlimb flexion when crossing the obstacle with contralesional Left limbs leading. At weeks 7-8 after hemisection, the proportion of complete clearance increased, Other responses decreased, and stumbling corrective reactions remained relatively unchanged. We found redistribution of weight support after hemisection, with reduced diagonal supports and increased homolateral supports, particularly on the left contralesional side. The main neural strategy for complete clearance in intact cats consisted of increased knee flexor activation. After hemisection, ipsilesional knee flexor activation remained, but it was insufficient or more variable as the limb approached the obstacle. Intact cats also increased their speed when stepping over an obstacle, an increase that disappeared after hemisection. The increase in complete clearance over time after hemisection paralleled the recovery of muscle activation patterns or new strategies. Our results suggest partial recovery of anticipatory control through neuroplastic changes in the locomotor control system.SIGNIFICANCE STATEMENT Most spinal cord injuries (SCIs) are incomplete and people can recover some walking functions. However, the main challenge for people with SCIs that do recover a high level of function is to produce a gait that can adjust to everyday occurrences, such as turning, stepping over an obstacle, etc. Here, we use the cat model to answer two basic questions: How does an animal negotiate an obstacle after an incomplete SCI and why does it fail to safely clear it? We show that the inability to clear an obstacle is because of improper activation of muscles that flex the knee. Animals recover a certain amount of function thanks to new strategies and changes within the nervous system.

Spinal Sensorimotor Circuits Play a Prominent Role in Hindlimb Locomotor Recovery after Staggered Thoracic Lateral Hemisections but Cannot Restore Posture and Interlimb Coordination during Quadrupedal Locomotion in Adult Cats.

Spinal sensorimotor circuits interact with supraspinal and peripheral inputs to generate quadrupedal locomotion. Ascending and descending spinal pathways ensure coordination between the forelimbs and hindlimbs. Spinal cord injury (SCI) disrupts these pathways. To investigate the control of interlimb coordination and hindlimb locomotor recovery, we performed two lateral thoracic hemisections on opposite sides of the cord (right T5-T6 and left T10-T11) at an interval of approximately two months in eight adult cats. In three cats, the spinal cord was transected at T12-T13. We collected electromyography (EMG) and kinematic data during quadrupedal and hindlimb-only locomotion before and after spinal lesions. We show that (1) cats spontaneously recover quadrupedal locomotion following staggered hemisections but require balance assistance after the second one, (2) coordination between the forelimbs and hindlimbs displays 2:1 patterns (two cycles of one forelimb within one hindlimb cycle) and becomes weaker and more variable after both hemisections, (3) left-right asymmetries in hindlimb stance and swing durations appear after the first hemisection and reverse after the second, and (4) support periods reorganize after staggered hemisections to favor support involving both forelimbs and diagonal limbs. Cats expressed hindlimb locomotion the day following spinal transection, indicating that lumbar sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered hemisections. These results reflect a series of changes in spinal sensorimotor circuits that allow cats to maintain and recover some level of quadrupedal locomotor functionality with diminished motor commands from the brain and cervical cord, although the control of posture and interlimb coordination remains impaired.

A sensory signal related to left-right symmetry modulates intra- and interlimb cutaneous reflexes during locomotion in intact cats.

Introduction: During locomotion, cutaneous reflexes play an essential role in rapidly responding to an external perturbation, for example, to prevent a fall when the foot contacts an obstacle. In cats and humans, cutaneous reflexes involve all four limbs and are task- and phase modulated to generate functionally appropriate whole-body responses. Methods: To assess task-dependent modulation of cutaneous interlimb reflexes, we electrically stimulated the superficial radial or superficial peroneal nerves in adult cats and recorded muscle activity in the four limbs during tied-belt (equal left-right speeds) and split-belt (different left-right speeds) locomotion. Results: We show that the pattern of intra- and interlimb cutaneous reflexes in fore- and hindlimbs muscles and their phase-dependent modulation were conserved during tied-belt and split-belt locomotion. Short-latency cutaneous reflex responses to muscles of the stimulated limb were more likely to be evoked and phase-modulated when compared to muscles in the other limbs. In some muscles, the degree of reflex modulation was significantly reduced during split-belt locomotion compared to tied-belt conditions. Split-belt locomotion increased the step-by-step variability of left-right symmetry, particularly spatially. Discussion: These results suggest that sensory signals related to left-right symmetry reduce cutaneous reflex modulation, potentially to avoid destabilizing an unstable pattern.

Spinal sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered thoracic lateral hemisections but cannot restore posture and interlimb coordination during quadrupedal locomotion in adult cats.

Spinal sensorimotor circuits interact with supraspinal and peripheral inputs to generate quadrupedal locomotion. Ascending and descending spinal pathways ensure coordination between the fore-and hindlimbs. Spinal cord injury disrupts these pathways. To investigate the control of interlimb coordination and hindlimb locomotor recovery, we performed two lateral thoracic hemisections placed on opposite sides of the cord (right T5-T6 and left T10-T11) at an interval of approximately two months in eight adult cats. In three cats, we then made a complete spinal transection caudal to the second hemisection at T12-T13. We collected electromyography and kinematic data during quadrupedal and hindlimb-only locomotion before and after spinal lesions. We show that 1) cats spontaneously recover quadrupedal locomotion following staggered hemisections but require balance assistance after the second one, 2) coordination between the fore-and hindlimbs displays 2:1 patterns and becomes weaker and more variable after both hemisections, 3) left-right asymmetries in hindlimb stance and swing durations appear after the first hemisection and reverse after the second, and 4) support periods reorganize after staggered hemisections to favor support involving both forelimbs and diagonal limbs. Cats expressed hindlimb locomotion the day following spinal transection, indicating that lumbar sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered hemisections. These results reflect a series of changes in spinal sensorimotor circuits that allow cats to maintain and recover some level of quadrupedal locomotor functionality with diminished motor commands from the brain and cervical cord, although the control of posture and interlimb coordination remains impaired. Significance Statement: Coordinating the limbs during locomotion depends on pathways in the spinal cord. We used a spinal cord injury model that disrupts communication between the brain and spinal cord by sectioning half of the spinal cord on one side and then about two months later, half the spinal cord on the other side at different levels of the thoracic cord in cats. We show that despite a strong contribution from neural circuits located below the second spinal cord injury in the recovery of hindlimb locomotion, the coordination between the forelimbs and hindlimbs weakens and postural control is impaired. We can use our model to test approaches to restore the control of interlimb coordination and posture during locomotion after spinal cord injury.

Changes in intra- and interlimb reflexes from hindlimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in the four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked cutaneous reflexes by electrically stimulating left and right superficial peroneal nerves before and after two thoracic lateral hemisections placed on opposite sides of the cord at 9-13 weeks interval in seven adult cats (4 males and 3 females). We recorded reflex responses in ten hindlimb and five forelimb muscles bilaterally. After the first (right T5-T6) and second (left T10-T11) hemisections, coordination of the fore- and hindlimbs was altered and/or became less consistent. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-latency reflex responses in homonymous and crossed hindlimb muscles largely remained unaffected after staggered hemisections. However, mid- and long-latency homonymous and crossed responses in both hindlimbs occurred less frequently after staggered hemisections. In forelimb muscles, homolateral and diagonal mid- and long-latency response occurrence significantly decreased after the first and second hemisections. In all four limbs, however, when present, short-, mid- and long-latency responses maintained their phase-dependent modulation. We also observed reduced durations of short-latency inhibitory homonymous responses in left hindlimb extensors early after the first hemisection and delayed short-latency responses in the right ipsilesional hindlimb after the first hemisection. Therefore, changes in cutaneous reflex responses correlated with impaired balance/stability and interlimb coordination during locomotion after spinal cord injury. Restoring reflex transmission could be used as a biomarker to facilitate locomotor recovery.

Modulation of the gait pattern during split-belt locomotion after lateral spinal cord hemisection in adult cats.

Most previous studies investigated the recovery of locomotion in animals and people with incomplete spinal cord injury (SCI) during relatively simple tasks (e.g., walking in a straight line on a horizontal surface or a treadmill). We know less about the recovery of locomotion after incomplete SCI in left-right asymmetric conditions, such as turning or stepping along circular trajectories. To investigate this, we collected kinematic and electromyography data during split-belt locomotion at different left-right speed differences before and after a right thoracic lateral spinal cord hemisection in nine adult cats. After hemisection, although cats still performed split-belt locomotion, we observed several changes in the gait pattern compared with the intact state at early (1-2 wk) and late (7-8 wk) time points. Cats with larger lesions showed new coordination patterns between the fore- and hindlimbs, with the forelimbs taking more steps. Despite this change in fore-hind coordination, cats maintained consistent phasing between the fore- and hindlimbs. Adjustments in cycle and phase (stance and swing) durations between the slow and fast sides allowed animals to maintain 1:1 left-right coordination. Periods of triple support involving the right (ipsilesional) hindlimb decreased in favor of quad support and triple support involving the other limbs. Step and stride lengths decreased with concurrent changes in the right fore- and hindlimbs, possibly to avoid interference. The above adjustments in the gait pattern allowed cats to retain the ability to locomote in asymmetric conditions after incomplete SCI. We discuss potential plastic neuromechanical mechanisms involved in locomotor recovery in these conditions.NEW & NOTEWORTHY Everyday locomotion often involves left-right asymmetries, when turning, walking along circular paths, stepping on uneven terrains, etc. To show how incomplete spinal cord injury affects locomotor control in asymmetric conditions, we collected data before and after a thoracic lateral spinal hemisection on a split-belt treadmill with one side stepping faster than the other. We show that adjustments in kinematics and muscle activity allowed cats to retain the ability to perform asymmetric locomotion after hemisection.

Control of Forelimb and Hindlimb Movements and Their Coordination during Quadrupedal Locomotion across Speeds in Adult Spinal Cats.

Coordinating the four limbs is critical for terrestrial mammalian locomotion. Thoracic spinal transection abolishes neural communication between the brain and spinal networks controlling hindlimb/leg movements. Several studies have shown that animal models of spinal transection (spinalization), such as mice, rats, cats, and dogs recover hindlimb locomotion with the forelimbs stationary or suspended. We know less on the ability to generate quadrupedal locomotion after spinal transection, however. We collected kinematic and electromyography data in four adult cats during quadrupedal locomotion at five treadmill speeds before (intact cats) and after low-thoracic spinal transection (spinal cats). We show that adult spinal cats performed quadrupedal treadmill locomotion and modulated their speed from 0.4 m/sec to 0.8 m/sec but required perineal stimulation. During quadrupedal locomotion, several compensatory strategies occurred, such as postural adjustments of the head and neck and the appearance of new coordination patterns between the forelimbs and hindlimbs, where the hindlimbs took more steps than the forelimbs. We also observed temporal changes, such as shorter forelimb cycle/swing durations and shorter hindlimb cycle/stance durations in the spinal state. Forelimb double support periods occupied a greater proportion of the cycle in the spinal state, and hindlimb stride length was shorter. Coordination between the forelimbs and hindlimbs was weakened and more variable in the spinal state. Changes in muscle activity reflected spatiotemporal changes in the locomotor pattern. Despite important changes in the pattern, our results indicate that biomechanical properties of the musculoskeletal system play an important role in quadrupedal locomotion and offset some of the loss in neural communication between networks controlling the forelimbs and hindlimbs after spinal transection.

State- and Condition-Dependent Modulation of the Hindlimb Locomotor Pattern in Intact and Spinal Cats Across Speeds.

Locomotion after complete spinal cord injury (spinal transection) in animal models is usually evaluated in a hindlimb-only condition with the forelimbs suspended or placed on a stationary platform and compared with quadrupedal locomotion in the intact state. However, because of the quadrupedal nature of movement in these animals, the forelimbs play an important role in modulating the hindlimb pattern. This raises the question: whether changes in the hindlimb pattern after spinal transection are due to the state of the system (intact versus spinal) or because the locomotion is hindlimb-only. We collected kinematic and electromyographic data during locomotion at seven treadmill speeds before and after spinal transection in nine adult cats during quadrupedal and hindlimb-only locomotion in the intact state and hindlimb-only locomotion in the spinal state. We attribute some changes in the hindlimb pattern to the spinal state, such as convergence in stance and swing durations at high speed, improper coordination of ankle and hip joints, a switch in the timing of knee flexor and hip flexor bursts, modulation of burst durations with speed, and incidence of bi-phasic bursts in some muscles. Alternatively, some changes relate to the hindlimb-only nature of the locomotion, such as paw placement relative to the hip at contact, magnitude of knee and ankle yield, burst durations of some muscles and their timing. Overall, we show greater similarity in spatiotemporal and EMG variables between the two hindlimb-only conditions, suggesting that the more appropriate pre-spinal control is hindlimb-only rather than quadrupedal locomotion.

Sensory Perturbations from Hindlimb Cutaneous Afferents Generate Coordinated Functional Responses in All Four Limbs during Locomotion in Intact Cats.

Coordinating the four limbs is an important feature of terrestrial mammalian locomotion. When the foot dorsum contacts an obstacle, cutaneous mechanoreceptors send afferent signals to the spinal cord to elicit coordinated reflex responses in the four limbs to ensure dynamic balance and forward progression. To determine how the locomotor pattern of all four limbs changes in response to a sensory perturbation evoked by activating cutaneous afferents from one hindlimb, we electrically stimulated the superficial peroneal (SP) nerve with a relatively long train at four different phases (mid-stance, stance-to-swing transition, mid-swing, and swing-to-stance transition) of the hindlimb cycle in seven adult cats. The largest functional effects of the stimulation were found at mid-swing and at the stance-to-swing transition with several changes in the ipsilateral hindlimb, such as increased activity in muscles that flex the knee and hip joints, increased joint flexion and toe height, increased stride/step lengths and increased swing duration. We also observed several changes in support periods to shift support from the stimulated hindlimb to the other three limbs. The same stimulation applied at mid-stance and the swing-to-stance transition produced more subtle changes in the pattern. We observed no changes in stride and step lengths in the ipsilateral hindlimb with stimulation in these phases. We did observe some slightly greater flexions at the knee and ankle joints with stimulation at mid-stance and a reduction in double support periods and increase in triple support. Our results show that correcting or preventing stumbling involves functional contributions from all four limbs.

Control of Mammalian Locomotion by Somatosensory Feedback.

When animals walk overground, mechanical stimuli activate various receptors located in muscles, joints, and skin. Afferents from these mechanoreceptors project to neuronal networks controlling locomotion in the spinal cord and brain. The dynamic interactions between the control systems at different levels of the neuraxis ensure that locomotion adjusts to its environment and meets task demands. In this article, we describe and discuss the essential contribution of somatosensory feedback to locomotion. We start with a discussion of how biomechanical properties of the body affect somatosensory feedback. We follow with the different types of mechanoreceptors and somatosensory afferents and their activity during locomotion. We then describe central projections to locomotor networks and the modulation of somatosensory feedback during locomotion and its mechanisms. We then discuss experimental approaches and animal models used to investigate the control of locomotion by somatosensory feedback before providing an overview of the different functional roles of somatosensory feedback for locomotion. Lastly, we briefly describe the role of somatosensory feedback in the recovery of locomotion after neurological injury. We highlight the fact that somatosensory feedback is an essential component of a highly integrated system for locomotor control. © 2021 American Physiological Society. Compr Physiol 11:1-71, 2021.

A Validation of Supervised Deep Learning for Gait Analysis in the Cat.

Gait analysis in cats and other animals is generally performed with custom-made or commercially developed software to track reflective markers placed on bony landmarks. This often involves costly motion tracking systems. However, deep learning, and in particular DeepLabCutTM (DLC), allows motion tracking without requiring placing reflective markers or an expensive system. The purpose of this study was to validate the accuracy of DLC for gait analysis in the adult cat by comparing results obtained with DLC and a custom-made software (Expresso) that has been used in several cat studies. Four intact adult cats performed tied-belt (both belts at same speed) and split-belt (belts operating at different speeds) locomotion at different speeds and left-right speed differences on a split-belt treadmill. We calculated several kinematic variables, such as step/stride lengths and joint angles from the estimates made by the two software and assessed the agreement between the two measurements using intraclass correlation coefficient or Lin's concordance correlation coefficient as well as Pearson's correlation coefficients. The results showed that DLC is at least as precise as Expresso with good to excellent agreement for all variables. Indeed, all 12 variables showed an agreement above 0.75, considered good, while nine showed an agreement above 0.9, considered excellent. Therefore, deep learning, specifically DLC, is valid for measuring kinematic variables during locomotion in cats, without requiring reflective markers and using a relatively low-cost system.

Inhibition and Facilitation of the Spinal Locomotor Central Pattern Generator and Reflex Circuits by Somatosensory Feedback From the Lumbar and Perineal Regions After Spinal Cord Injury.

Somatosensory feedback from peripheral receptors dynamically interacts with networks located in the spinal cord and brain to control mammalian locomotion. Although somatosensory feedback from the limbs plays a major role in regulating locomotor output, those from other regions, such as lumbar and perineal areas also shape locomotor activity. In mammals with a complete spinal cord injury, inputs from the lumbar region powerfully inhibit hindlimb locomotion, while those from the perineal region facilitate it. Our recent work in cats with a complete spinal cord injury shows that they also have opposite effects on cutaneous reflexes from the foot. Lumbar inputs increase the gain of reflexes while those from the perineal region decrease it. The purpose of this review is to discuss how somatosensory feedback from the lumbar and perineal regions modulate the spinal locomotor central pattern generator and reflex circuits after spinal cord injury and the possible mechanisms involved. We also discuss how spinal cord injury can lead to a loss of functional specificity through the abnormal activation of functions by somatosensory feedback, such as the concurrent activation of locomotion and micturition. Lastly, we discuss the potential functions of somatosensory feedback from the lumbar and perineal regions and their potential for promoting motor recovery after spinal cord injury.

Cutaneous inputs from perineal region facilitate spinal locomotor activity and modulate cutaneous reflexes from the foot in spinal cats.

It is well known that mechanically stimulating the perineal region potently facilitates hindlimb locomotion and weight support in mammals with a spinal transection (spinal mammals). However, how perineal stimulation mediates this excitatory effect is poorly understood. We evaluated the effect of mechanically stimulating (vibration or pinch) the perineal region on ipsilateral (9-14 ms onset) and contralateral (14-18 ms onset) short-latency cutaneous reflex responses evoked by electrically stimulating the superficial peroneal or distal tibial nerve in seven adult spinal cats where hindlimb movement was restrained. Cutaneous reflexes were evoked before, during, and after mechanical stimulation of the perineal region. We found that vibration or pinch of the perineal region effectively triggered rhythmic activity, ipsilateral and contralateral to nerve stimulation. When electrically stimulating nerves, adding perineal stimulation modulated rhythmic activity by decreasing cycle and burst durations and by increasing the amplitude of flexors and extensors. Perineal stimulation also disrupted the timing of the ipsilateral rhythm, which had been entrained by nerve stimulation. Mechanically stimulating the perineal region decreased ipsilateral and contralateral short-latency reflex responses evoked by cutaneous inputs, a phenomenon we observed in muscles crossing different joints and located in different limbs. The results suggest that the excitatory effect of perineal stimulation on locomotion and weight support is mediated by increasing the excitability of central pattern-generating circuitry and not by increasing excitatory inputs from cutaneous afferents of the foot. Our results are consistent with a state-dependent modulation of reflexes by spinal interneuronal circuits.

The Spinal Control of Backward Locomotion.

Animal locomotion requires changing direction, from forward to backward. Here, we tested the hypothesis that sensorimotor circuits within the spinal cord generate backward locomotion and adjust it to task demands. We collected kinematic and electromyography (EMG) data during forward and backward locomotion at different treadmill speeds before and after complete spinal transection in six adult cats (three males and three females). After spinal transection, five/six cats performed backward locomotion, which required tonic somatosensory input in the form of perineal stimulation. One spinal cat performed forward locomotion but not backward locomotion while two others stepped backward but not forward. Spatiotemporal adjustments to increasing speed were similar in intact and spinal cats during backward locomotion and strategies were similar to forward locomotion, with shorter cycle and stance durations and longer stride lengths. Patterns of muscle activations, including muscle synergies, were similar for forward and backward locomotion in spinal cats. Indeed, we identified five muscle synergies that were similar during forward and backward locomotion. Lastly, spinal cats also stepped backward on a split-belt treadmill, with the left and right hindlimbs stepping at different speeds. Therefore, our results show that spinal sensorimotor circuits generate backward locomotion but require additional excitability compared with forward locomotion. Similar strategies for speed modulation and similar patterns of muscle activations and muscle synergies during forward and backward locomotion are consistent with a shared spinal locomotor network, with sensory feedback from the limbs controlling the direction.SIGNIFICANCE STATEMENT Animal locomotion requires changing direction, including forward, sideways and backward. This paper shows that the center controlling locomotion within the spinal cord can produce a backward pattern when instructed by sensory signals from the limbs. However, the spinal locomotor network requires greater excitability to produce backward locomotion compared with forward locomotion. The paper also shows that the spinal network controlling locomotion in the forward direction also controls locomotion in the backward direction.

On the Organization of the Locomotor CPG: Insights From Split-Belt Locomotion and Mathematical Modeling.

Rhythmic limb movements during locomotion are controlled by central pattern generator (CPG) circuits located in the spinal cord. It is considered that these circuits are composed of individual rhythm generators (RGs) for each limb interacting with each other through multiple commissural and long propriospinal circuits. The organization and operation of each RG are not fully understood, and different competing theories exist about interactions between its flexor and extensor components, as well as about left-right commissural interactions between the RGs. The central idea of circuit organization proposed in this study is that with an increase of excitatory input to each RG (or an increase in locomotor speed) the rhythmogenic mechanism of the RGs changes from "flexor-driven" rhythmicity to a "classical half-center" mechanism. We test this hypothesis using our experimental data on changes in duration of stance and swing phases in the intact and spinal cats walking on the ground or tied-belt treadmills (symmetric conditions) or split-belt treadmills with different left and right belt speeds (asymmetric conditions). We compare these experimental data with the results of mathematical modeling, in which simulated CPG circuits operate in similar symmetric and asymmetric conditions with matching or differing control drives to the left and right RGs. The obtained results support the proposed concept of state-dependent changes in RG operation and specific commissural interactions between the RGs. The performed simulations and mathematical analysis of model operation under different conditions provide new insights into CPG network organization and limb coordination during locomotion.