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bioRxiv · 10.1101/2020.07.17.205351

On the organization of the locomotor CPG: insights from split-belt locomotion and mathematical modeling

Latash, E. M.·Lecomte, C. G.·Danner, S. M.·Frigon, A.·Rybak, I. A.·Molkov, Y. I.
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Abstract

Rhythmic limb movements during locomotion are controlled by a 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 RGs (or an increase in locomotor speed) the rhythmogenic mechanism within 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. Key Point SummaryO_LILimb movements during locomotion are controlled by neural circuits located within the spinal cord. These circuits include rhythm generators (RGs) controlling each limb interacting through multiple commissural pathways. C_LIO_LIThe organization and operation of spinal RGs are not fully understood, and different competing concepts exists. We suggest that the operation of RGs is state-dependent, so that with an increase of external excitation the rhythmogenesis changes from "flexor-driven" oscillations to a "classical half-center" mechanism. C_LIO_LIA mathematical model of spinal circuits representing bilaterally-interacting RGs has been developed based on the above suggestion and used to interpret experimental data from intact and spinal cats walking on the ground or tied-belt treadmills (symmetric conditions) as well as on split-belt treadmills with different left and right belt speeds (asymmetric conditions). C_LIO_LIThe performed simulations and mathematical analysis of the model under different conditions provide new insights into operation of spinal circuits and limb coordination during locomotion. C_LI

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Latash, E. M., Lecomte, C. G., Danner, S. M., Frigon, A., Rybak, I. A., Molkov, Y. I.. 2020-07-18. On the organization of the locomotor CPG: insights from split-belt locomotion and mathematical modeling. https://doi.org/10.1101/2020.07.17.205351

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