Comparison of operation of spinal locomotor networks activated by supraspinal commands and by epidural stimulation of the spinal cord in cats

Abstract

Key points Epidural electrical stimulation (ES) of the spinal cord restores/improves locomotion in patients. ES‐evoked locomotor movements differ to some extent from the normal ones. Operation of the locomotor network during ES is unknown. We compared the activity of individual spinal neurons during locomotion initiated by signals from the brainstem and by ES. We demonstrated that the spinal network generating locomotion under each of the two conditions is formed by the same neurons. A part of this network operates similarly under the two conditions, suggesting that it is essential for generation of locomotion under both conditions. Another part of this network operates differently under the two conditions, suggesting that it is responsible for differences in the movement kinematics observed under the two conditions. Abstract Locomotion is a vital motor function for both animals and humans. Epidural electrical stimulation (ES) of the spinal cord is used to restore/improve locomotor movements in patients. However, operation of locomotor networks during ES has never been studied. Here we compared the activity of individual spinal neurons recorded in decerebrate cats of either sex during locomotion initiated by supraspinal commands (caused by stimulation of the mesencephalic locomotor region, MLR) and by ES. We found that under both conditions, the same neurons had modulation of their activity related to the locomotor rhythm, suggesting that the network generating locomotion under the two conditions is formed by the same neurons. About 40% of these neurons had stable modulation (i.e. small dispersion of their activity phase in sequential cycles), as well as a similar phase and shape of activity burst in MLR‐ and ES‐evoked locomotor cycles. We suggest that these neurons form a part of the locomotor network that operates similarly under the two conditions, and are critical for generation of locomotion. About 23% of the modulated neurons had stable modulation only during MLR‐evoked locomotion. We suggest that these neurons are responsible for some differences in kinematics of MLR‐ and ES‐evoked locomotor movements. Finally, 25% of the modulated neurons had unstable modulation during both MLR‐ and ES‐evoked locomotion. One can assume that these neurons contribute to maintenance of the excitability level of locomotor networks necessary for generation of stepping, or belong to postural networks, activated simultaneously with locomotor networks by both MLR stimulation and ES.

Activity of Spinal Interneurons during Forward and Backward Locomotion

“…These results are similar to those described previously (Musienko et al, 2012(Musienko et al, , 2020Merkulyeva et al, 2018). However, it should be noted that the kinematics of FW and BW caused by ES differ, to some extent, from those observed in intact cats .…”

“…Surgical procedures. The surgical procedures were similar to those in our previous studies (Merkulyeva et al, 2018;Musienko et al, 2020). The cats were deeply anesthetized with isoflurane (2-4%) delivered in O 2 .…”

“…The experimental design (Fig. 1A) was similar to that used in our previous study (Musienko et al, 2020). The head, the vertebral column, and the pelvis of the decerebrate cat were fixed in a rigid frame.…”

“…If the neuron with complementary sensory inputs had the phase of modulation similar under the two conditions, it was suggested that modulation of this neuron during locomotion can be explained by sensory feedback from the hindlimbs. If the phases of modulation largely overlapped under the two conditions (the phase of the burst in one of the conditions was within the phase of the burst observed in another condition; Musienko et al, 2020), it was suggested that sensory feedback from the hindlimbs can potentially contribute to modulation of these neurons during locomotion. Finally, if the phases of modulation under the two conditions were different, it was suggested that locomotor modulation of this neuron cannot be explained by sensory feedback from the limb.…”

Toward Assessing the Functional Connectivity of Spinal Neurons

“…This work has been done in several species during a relatively small range of behaviors. Most of these have focused on quantifying interneuronal activity during endogenous behaviors, such as locomotion in the cat ( AuYong et al, 2011a , b ; Dominguez-Rodriguez et al, 2020 ; Musienko et al, 2020 ; McMahon et al, 2021 ), scratching in the turtle ( Radosevic et al, 2019 ), or under anesthesia in the rat ( McPherson and Bandres, 2021 ). While such behaviors are critical to understand input-output properties within and between interneurons and motoneurons, these relationships are difficult to extract in an intrinsically oscillating circuit.…”