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

   https://doi.org/10.7554/eLife.98841  

   Rybak, Ilya A; Shevtsova, Natalia A; Markin, Sergey N; Prilutsky, Boris I; Frigon, Alain (October 2024, eLife)

   Smith, Jeffrey C (Ed.)

   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 model predicts that 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. 

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2. Operation of spinal sensorimotor circuits controlling phase durations during tied-belt and split-belt locomotion after a lateral thoracic hemisection

   https://doi.org/10.7554/eLife.103504  

   Rybak, Ilya A; Shevtsova, Natalia A; Audet, Johannie; Yassine, Sirine; Markin, Sergey N; Prilutsky, Boris I; Frigon, Alain (January 2025, eLife)

   Smith, Jeffrey C (Ed.)

   Locomotion is controlled by spinal circuits that interact with supraspinal drives and sensory feedback from the limbs. These sensorimotor interactions are disrupted following spinal cord injury. The thoracic lateral hemisection represents an experimental model of an incomplete spinal cord injury, where connections between the brain and spinal cord are abolished on one side of the cord. To investigate the effects of such an injury on the operation of the spinal locomotor network, we used our computational model of cat locomotion recently published ineLife(Rybak et al., 2024) to investigate and predict changes in cycle and phase durations following a thoracic lateral hemisection during treadmill locomotion in tied-belt (equal left-right speeds) and split-belt (unequal left-right speeds) conditions. In our simulations, the ‘hemisection’ was always applied to the right side. Based on our model, we hypothesized that following hemisection the contralesional (‘intact’, left) side of the spinal network is mostly controlled by supraspinal drives, whereas the ipsilesional (‘hemisected’, right) side is mostly controlled by somatosensory feedback. We then compared the simulated results with those obtained during experiments in adult cats before and after a mid-thoracic lateral hemisection on the right side in the same locomotor conditions. Our experimental results confirmed many effects of hemisection on cat locomotion predicted by our simulations. We show that having the ipsilesional hindlimb step on the slow belt, but not the fast belt, during split-belt locomotion substantially reduces the effects of lateral hemisection. The model provides explanations for changes in temporal characteristics of hindlimb locomotion following hemisection based on altered interactions between spinal circuits, supraspinal drives, and somatosensory feedback. 

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3. Contribution of Afferent Feedback to Adaptive Hindlimb Walking in Cats: A Neuromusculoskeletal Modeling Study

   https://doi.org/10.3389/fbioe.2022.825149  

   Kim, Yongi; Aoi, Shinya; Fujiki, Soichiro; Danner, Simon M.; Markin, Sergey N.; Ausborn, Jessica; Rybak, Ilya A.; Yanagihara, Dai; Senda, Kei; Tsuchiya, Kazuo (April 2022, Frontiers in Bioengineering and Biotechnology)

   Mammalian locomotion is generated by central pattern generators (CPGs) in the spinal cord, which produce alternating flexor and extensor activities controlling the locomotor movements of each limb. Afferent feedback signals from the limbs are integrated by the CPGs to provide adaptive control of locomotion. Responses of CPG-generated neural activity to afferent feedback stimulation have been previously studied during fictive locomotion in immobilized cats. Yet, locomotion in awake, behaving animals involves dynamic interactions between central neuronal circuits, afferent feedback, musculoskeletal system, and environment. To study these complex interactions, we developed a model simulating interactions between a half-center CPG and the musculoskeletal system of a cat hindlimb. Then, we analyzed the role of afferent feedback in the locomotor adaptation from a dynamic viewpoint using the methods of dynamical systems theory and nullcline analysis. Our model reproduced limb movements during regular cat walking as well as adaptive changes of these movements when the foot steps into a hole. The model generates important insights into the mechanism for adaptive locomotion resulting from dynamic interactions between the CPG-based neural circuits, the musculoskeletal system, and the environment. 

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4. Resilience of neural networks for locomotion

   https://doi.org/10.1113/JP279214  

   Haspel, Gal; Severi, Kristen E.; Fauci, Lisa J.; Cohen, Netta; Tytell, Eric D.; Morgan, Jennifer R. (August 2021, The Journal of Physiology)

   null (Ed.)

   Locomotion is an essential behaviour for the survival of all animals. The neural circuitry underlying locomotion is therefore highly robust to a wide variety of perturbations, including injury and abrupt changes in the environment. In the short term, fault tolerance in neural networks allows locomotion to persist immediately after mild to moderate injury. In the longer term, in many invertebrates and vertebrates, neural reorganization including anatomical regeneration can restore locomotion after severe perturbations that initially caused paralysis. Despite decades of research, very little is known about the mechanisms underlying locomotor resilience at the level of the underlying neural circuits and coordination of central pattern generators (CPGs). Undulatory locomotion is an ideal behaviour for exploring principles of circuit organization, neural control and resilience of locomotion, offering a number of unique advantages including experimental accessibility and modelling tractability. In comparing three well-characterized undulatory swimmers, lampreys, larval zebrafish and Caenorhabditis elegans, we find similarities in the manifestation of locomotor resilience. To advance our understanding, we propose a comparative approach, integrating experimental and modelling studies, that will allow the field to begin identifying shared and distinct solutions for overcoming perturbations to persist in orchestrating this essential behaviour. 

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5. Inhibition of knee joint sensory afferents alters covariation across strides between quadriceps muscles during locomotion

   https://doi.org/10.1152/japplphysiol.00591.2022  

   Alessandro, Cristiano; Prashara, Adarsh; Tentler, David P.; Tresch, Matthew C. (April 2023, Journal of Applied Physiology)

   Sport-related injuries to articular structures often alter the sensory information conveyed by joint structures to the nervous system. However, the role of joint sensory afferents in motor control is still unclear. Here, we evaluate the role of knee joint sensory afferents in the control of quadriceps muscles, hypothesizing that such sensory information modulates control strategies that limit patellofemoreal joint loading. We compared locomotor kinematics and muscle activity before and after inhibition of knee sensory afferents by injection of lidocaine into the knee capsule of rats. We evaluated whether this inhibition reduced the strength of correlation between the activity of vastus medialis (VM) and vastus lateralis (VL) both across strides and within each stride, coordination patterns that limit net mediolateral patellofemoral forces. We also evaluated whether this inhibition altered correlations among the other quadriceps muscle activity, the time-profiles of individual EMG envelopes, or movement kinematics. Neither the EMG envelopes nor limb kinematics was affected by the inhibition of knee sensory afferents. This perturbation also did not affect the correlations between VM and VL, suggesting that the regulation of patellofemoral joint loading is mediated by different mechanisms. However, inhibition of knee sensory afferents caused a significant reduction in the correlation between vastus intermedius (VI) and both VM and VL across, but not within, strides. Knee joint sensory afferents may therefore modulate the coordination between the vasti muscles but only at coarse time scales. Injuries compromising joint afferents might result in altered muscle coordination, potentially leading to persistent internal joint stresses and strains. NEW & NOTEWORTHY Sensory afferents originating from knee joint receptors provide the nervous system with information about the internal state of the joint. In this study, we show that these sensory signals are used to modulate the covariations among the activity of a subset of vasti muscles across strides of locomotion. Sport-related injuries that damage joint receptors may therefore compromise these mechanisms of muscle coordination, potentially leading to persistent internal joint stresses and strains. 

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