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

Abstract

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 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 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 (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.Significance StatementCoordinating 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

“…We recently described changes in the quadrupedal locomotor pattern after staggered thoracic lateral hemisections, including six cats of the present study (Audet et al., 2023). Briefly, cats spontaneously recovered quadrupedal locomotion following staggered hemisections but required balance assistance after the second one.…”

“…The investigators understand the ethical principles under which the journal operates and our work complies with this animal ethics checklist. In order to maximize the scientific output of each animal, they were used in other studies to investigate different scientific questions, some of which have been published (Audet et al., 2023; Lecomte et al., 2022, 2023; Mari et al., 2023; Merlet et al., 2022).…”

“…Cardiac arrest was confirmed using a stethoscope to determine the death of the animal. Spinal cords were then harvested for histological analysis (Audet et al., 2023; Lecomte et al., 2023).…”

“…We stimulated the SP nerve before, after a mid‐thoracic lateral hemisection on the right side and then after a second lateral hemisection on the left side a few spinal segments caudal to the first hemisection 9–13 weeks later. This staggered hemisections paradigm disrupts direct ascending and descending spinal pathways that communicate between the brain/cervical cord and lumbosacral circuits, severely impairing fore–hind coordination (Audet et al., 2023; Courtine et al., 2008; Cowley et al., 2015; Jane et al., 1964; Kato et al., 1984, 1985; Stelzner & Cullen, 1991; Van Den Brand et al., 2012). Here, we used this paradigm to probe changes in neural pathways projecting to the four limbs and to determine their potential role in forelimb–hindlimb coordination.…”

Simultaneous control of forward and backward locomotion by spinal sensorimotor circuits

“…For phase duration–cycle duration relationships, we include cycles with 1:1 and 2+:1 coordination. Rayleigh's test was performed to determine if phase intervals were randomly distributed, as described (Kjaerulff & Kiehn, 1996; Thibaudier et al., 2017; Audet et al., 2023). Briefly, we calculated the r ‐value to measure the dispersion of phase interval values around the mean, with a value of 1 indicating a perfect concentration in one direction, and a value of 0 indicating uniform dispersion.…”