The recovery of standing and locomotion after spinal cord injury does not require task-specific training

Abstract

After complete spinal cord injury, mammals, including mice, rats and cats, recover hindlimb locomotion with treadmill training. The premise is that sensory cues consistent with locomotion reorganize spinal sensorimotor circuits. Here, we show that hindlimb standing and locomotion recover after spinal transection in cats without task-specific training. Spinal-transected cats recovered full weight bearing standing and locomotion after five weeks of rhythmic manual stimulation of triceps surae muscles (non-specific training) and without any intervention. Moreover, cats modulated locomotor speed and performed split-belt locomotion six weeks after spinal transection, functions that were not trained or tested in the weeks prior. This indicates that spinal networks controlling standing and locomotion and their interactions with sensory feedback from the limbs remain largely intact after complete spinal cord injury. We conclude that standing and locomotor recovery is due to the return of neuronal excitability within spinal sensorimotor circuits that do not require task-specific activity-dependent plasticity.

Cutaneous inputs from perineal region facilitates and modulates spinal locomotor activity and reduces cutaneous reflexes from the foot in spinal cats

“…Before and after experiments, cats were housed and fed in a dedicated room within the animal care facility of the Faculty of Medicine and Health Sciences at the Université de Sherbrooke. As part of our effort to maximize the scientific output of each animal, all animals were used in previous studies to answer other scientific questions (Harnie et al, 2019;Merlet et al, 2020).…”

“…We performed implantation and spinal transection surgeries under aseptic conditions in an operating room with sterilized equipment, as described previously (Harnie et al 2019;Merlet et al 2020). Briefly, an intramuscular injection containing butorphanol (0.4 mg/kg), acepromazine (0.1 mg/kg), glycopyrrolate (0.01 mg/kg) and ketamine/diazepam (0.11 ml/kg in a 1:1 ratio, i.m.)…”

“…Preclinical models of spinal transection (i.e. spinal animals), such as cats, rats and mice, recover hindlimb locomotion with treadmill training (Shurrager & Dykman, 1951;Lovely et al, 1986Lovely et al, , 1990; Hodgson et al, 1994;Belanger et al, 1996;de Leon et al, 1998;De Leon et al, 1999;Leblond et al, 2003;Cha et al, 2007;Sławińska et al, 2012) or, as shown recently, without task-specific training (Harnie et al, 2019). This is due to the presence of a network of neurons located within the lumbar cord that produces the basic hindlimb locomotor pattern, the so-called central pattern generator (CPG) (McCrea & Rybak, 2008;Rossignol & Frigon, 2011;Kiehn, 2016).…”

“…In contrast, tonic stimulation of the skin of the perineal region (scrotum, vulva, base of the tail and inguinal fold) facilitates hindlimb locomotion in spinal mammals. For decades, perineal stimulation has been used to initiate fictive locomotion in acute spinal decerebrate curarized preparations treated with clonidine, an α2-noradrenergic agonist (Forssberg & Grillner, 1973;Pearson & Rossignol, 1991;Pearson et al, 1992;McCrea et al, 1995;Bennett et al, 1996) and to facilitate or reinforce hindlimb locomotion in chronic spinal mammals Belanger et al, 1996;Leblond et al, 2003;Langlet et al, 2005;Hochman, 2012;Alluin et al, 2015;Harnie et al, 2019). Stimulating the skin of the perineal region can trigger a wellcoordinated pattern of hindlimb locomotion by increasing spinal neuronal excitability through an undefined mechanism (Pearson & Rossignol, 1991).…”

“…Stimulating the skin of the perineal region can trigger a wellcoordinated pattern of hindlimb locomotion by increasing spinal neuronal excitability through an undefined mechanism (Pearson & Rossignol, 1991). Harnie et al (2019) proposed that the increase in spinal neuronal excitability provided by tonic perineal stimulation replaces monoaminergic drive from the brainstem. Indeed, several pharmacological studies demonstrated that injecting noradrenergic agonists in spinal cats (Forssberg & Grillner, 1973; Chau et al, 1998aChau et al, , 1998b or serotonergic agonists in spinal mice or rats (Kim et al, 2001;Antri et al, 2002Antri et al, , 2005Sławińska et al, 2012) facilitates hindlimb locomotion by increasing spinal neuronal excitability.…”