Papers by Serge Rossignol

The Journal of Neuroscience, Apr 9, 2008
The re-expression of hindlimb locomotion after complete spinal cord injuries (SCIs) is caused by ... more The re-expression of hindlimb locomotion after complete spinal cord injuries (SCIs) is caused by the presence of a spinal central pattern generator (CPG) for locomotion. After partial SCI, however, the role of this spinal CPG in the recovery of hindlimb locomotion in the cat remains mostly unknown. In the present work, we devised a dual-lesion paradigm to determine its possible contribution after partial SCI. After a partial section of the left thoracic segment T10 or T11, cats gradually recovered voluntary quadrupedal locomotion. Then, a complete transection was performed two to three segments more caudally (T13-L1) several weeks after the first partial lesion. Cats that received intensive treadmill training after the partial lesion expressed bilateral hindlimb locomotion within hours of the complete lesion. Untrained cats however showed asymmetrical hindlimb locomotion with the limb on the side of the partial lesion walking well before the other hindlimb. Thus, the complete spinalization revealed that the spinal CPG underwent plastic changes after the partial lesions, which were shaped by locomotor training. Over time, with further treadmill training, the asymmetry disappeared and a bilateral locomotion was reinstated. Therefore, although remnant intact descending pathways must contribute to voluntary goal-oriented locomotion after partial SCI, the recovery and re-expression of the hindlimb locomotor pattern mostly results from intrinsic changes below the lesion in the CPG and afferent inputs.
Faculty of 1000 evaluation for A clinical prediction rule for ambulation outcomes after traumatic spinal cord injury: a longitudinal cohort study
F1000 - Post-publication peer review of the biomedical literature, 2011
Faculty of 1000 evaluation for Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury
F1000 - Post-publication peer review of the biomedical literature, 2007
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2012
Pradat, D é partement des Maladies du Syst è me Nerveux, Groupe hospitalier Piti é -Salp ê tri è ... more Pradat, D é partement des Maladies du Syst è me Nerveux, Groupe hospitalier Piti é -Salp ê tri è re, 47 Ϫ 83, Boulevard de l'H ô pital,

The Journal of Neuroscience, Aug 8, 2012
After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be rev... more After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later. Cats were not treadmill trained during the hemispinal period. After spinalization, 5 of 9 cats were not trained and served as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week for 3 weeks. Using detailed kinematic analyses, we showed that, without training, the asymmetrical state of locomotion induced by the hemisection was retained durably after the subsequent spinalization. By contrast, training cats after spinalization induced a reversal of the left/right asymmetries, suggesting that new plastic changes occurred within the spinal cord through locomotor training. Moreover, training was shown to improve the kinematic parameters and the performance of the hindlimb on the previously hemisected side. These results indicate that spinal locomotor circuits, previously modified by past experience such as required for adaptation to the hemisection, can remarkably respond to subsequent locomotor training and improve bilateral locomotor kinematics, clearly showing the benefits of locomotor training in the spinal state.

Philosophical Transactions of the Royal Society B, Aug 4, 2006
This review discusses some aspects of plasticity of connections after spinal injury in adult anim... more This review discusses some aspects of plasticity of connections after spinal injury in adult animal models as a basis for functional recovery of locomotion. After reviewing some pitfalls that must be avoided when claiming functional recovery and the importance of a conceptual framework for the control of locomotion, locomotor recovery after spinal lesions, mainly in cats, is summarized. It is concluded that recovery is partly due to plastic changes within the existing spinal locomotor networks. Locomotor training appears to change the excitability of simple reflex pathways as well as more complex circuitry. The spinal cord possesses an intrinsic capacity to adapt to lesions of central tracts or peripheral nerves but, as a rule, adaptation to lesions entails changes at both spinal and supraspinal levels. A brief summary of the spinal capacity of the rat, mouse and human to express spinal locomotor patterns is given, indicating that the concepts derived mainly from work in the cat extend to other adult mammals. It is hoped that some of the issues presented will help to evaluate how plasticity of existing connections may combine with and potentiate treatments designed to promote regeneration to optimize remaining motor functions.
Journal of Neurophysiology, 2020
The recovery of quadrupedal treadmill locomotion after a large bilateral contusion at the low tho... more The recovery of quadrupedal treadmill locomotion after a large bilateral contusion at the low thoracic T10 spinal level and the ability to negotiate obstacles were studied for 5 wk in 16 cats. Ten cats were further completely spinalized at T13 and were found to walk with the hindlimbs within 24–72 h. We conclude that the extent of locomotor recovery after large spinal contusions hinges both on remnant supraspinal pathways and on a spinal pattern generator.

Plasticity of Stepping Rhythms in the Intact and Injured Mammalian Spinal Cord
Oxford Research Encyclopedia of Neuroscience, 2017
The spinal cord is a prime example of how the central nervous system has evolved to execute and r... more The spinal cord is a prime example of how the central nervous system has evolved to execute and retain movements adapted to the environment. This results from the evolution of inborn intrinsic spinal circuits modified continuously by repetitive interactions with the outside world, as well as by developing internal needs or goals. This article emphasizes the underlying neuroplastic spinal mechanisms through observations of normal animal adaptive locomotor behavior in different imposed conditions. It further explores the motor spinal capabilities after various types of lesions to the spinal cord and the potential mechanisms underlying the spinal changes occurring after these lesions, leading to recovery of function. Together, these observations strengthen the idea of the immense potential of the motor rehabilitation approach in humans with spinal cord injury since extrinsic interventions (training, pharmacology, and electrical stimulation) can modulate and optimize remnant motor funct...
Faculty of 1000 evaluation for Functional organization of locomotor interneurons in the ventral lumbar spinal cord of the newborn rat
F1000 - Post-publication peer review of the biomedical literature, 2012

F1000 - Post-publication peer review of the biomedical literature, 2009
The primary control of spinal motoneurone excitability is mediated by descending monoaminergic sy... more The primary control of spinal motoneurone excitability is mediated by descending monoaminergic systems, which have diffuse effects on multiple motor pools. Much of the sensory input evoked by movement is also distributed broadly to multiple joints. The muscle spindle Ia afferent system, however, is sharply focused, with Ia excitation restricted to close synergists and Ia reciprocal inhibition only shared between antagonists acting at a single joint. We studied the interaction of neuromodulatory and sensory inputs in determining the movement-related receptive field (MRRF) of motoneurones during passive joint movements of the cat hindlimb. In a decerebrate preparation with tonic monoaminergic input to the cord, the MRRFs tended to be focused for the ankle and knee extensor motor pools studied. Ankle rotation produced larger synaptic currents in ankle extensors than knee or hip rotations and knee rotation dominated input to the knee extensors. The persistent inward current (PIC) in motoneurone dendrites, which is facilitated by monoaminergic input, amplified the MRRF about 2-fold, consistent with its effects on other inputs. Acute spinal transaction markedly broadened MRRFs, with hip rotation generating large currents in both ankle and knee extensors. Spinalization also eliminated amplification of MRRFs, as expected from elimination of descending monoaminergic input. Ia reciprocal inhibition is very effective in suppressing dendritic PICs and thus provides a local and specific PIC control system to oppose the diffuse PIC facilitation from descending monoaminergic systems. The focused MRRF seen in the intact cord state would allow reciprocal inhibition to fulfil this role without undue interference from multijoint input from other afferent systems.

NeuroImage, 2011
One goal of in vivo neuroimaging is the detection of neurodegenerative processes and anatomical r... more One goal of in vivo neuroimaging is the detection of neurodegenerative processes and anatomical reorganizations after spinal cord (SC) injury. Non-invasive examination of white matter fibers in the living SC can be conducted using magnetic resonance diffusion-weighted imaging. However, this technique is challenging at the spinal level due to the small cross-sectional size of the cord and the presence of physiological motion and susceptibility artifacts. In this study, we acquired in vivo high angular resolution diffusion imaging (HARDI) data at 3T in cats submitted to partial SC injury. Cats were imaged before, 3 and 21 days after injury. Spatial resolution was enhanced to 1.5 × 1.5 × 1 mm 3 using super-resolution technique and distortions were corrected using the reversed gradient method. Tractography-derived regions of interest were generated in the dorsal, ventral, right and left quadrants, to evaluate diffusion tensor imaging (DTI) and Q-Ball imaging metrics with regards to their sensitivity in detecting primary and secondary lesions. A threeway ANOVA tested the effect of session (intact, D3, D21), cross-sectional region (left, right, dorsal and ventral) and rostrocaudal location. Significant effect of session was found for FA (P b 0.001), GFA (P b 0.05) and radial diffusivity (P b 0.001). Post-hoc paired T-test corrected for multiple comparisons showed significant changes at the lesion epicenter (P b 0.005). More interestingly, significant changes were also found several centimeters from the lesion epicenter at both 3 and 21 days. This decrease was specific to the type of fibers, i.e., rostrally to the lesion on the dorsal aspect of the cord and caudally to the lesion ipsilaterally, suggesting the detection of Wallerian degeneration.

Medical Image Analysis, 2007
Due to its non-invasive nature and low cost, diffuse optical imaging (DOI) is becoming a commonly... more Due to its non-invasive nature and low cost, diffuse optical imaging (DOI) is becoming a commonly used technique to assess functional activation in the brain. When imaging with DOI, two major issues arise in the data analysis: (i) the separation of noise of physiological origin and the recovery of the functional response; (ii) the tomographic image reconstruction problem. This paper focuses on the first issue. Although the general linear model (GLM) has been extensively used in functional magnetic resonance imaging (fMRI), DOI has mostly relied on filtering and averaging of raw data to recover brain functional activation. This is mainly due to the high temporal resolution of DOI which implies a new design of the drift basis modelling physiology. In this paper, we provide (i) a filtering method based on cosine functions that is more adapted than standard averaging techniques for DOI specifically; (ii) a new mode-locking technique to recover small signals and locate them temporally with high precision (shift method). Results on real data show the capability of the shift method to retrieve HbR and HbO 2 peak locations.
Kinematic Study of Locomotor Recovery after Spinal Cord Clip Compression Injury in Rats
Journal of Neurotrauma, 2011

A dual spinal cord lesion paradigm to study spinal locomotor plasticity in the cat
Annals of the New York Academy of Sciences, 2013
After a complete spinal cord injury (SCI) at the lowest thoracic level (T13), adult cats trained ... more After a complete spinal cord injury (SCI) at the lowest thoracic level (T13), adult cats trained to walk on a treadmill can recover hindlimb locomotion within 2-3 weeks, resulting from the activity of a spinal circuitry termed the central pattern generator (CPG). The role of this spinal circuitry in the recovery of locomotion after partial SCIs, when part of descending pathways can still access the CPG, is not yet fully understood. Using a dual spinal lesion paradigm (first hemisection at T10 followed three weeks after by a complete spinalization at T13), we showed that major changes occurred in this locomotor spinal circuitry. These plastic changes at the spinal cord level could participate in the recovery of locomotion after partial SCI. This short review describes the main findings of this paradigm in adult cats.

Locomotor capacities after complete and partial lesions of the spinal cord
Acta neurobiologiae experimentalis, 1996
This paper first reviews some of the observations made on the locomotor capabilities of several a... more This paper first reviews some of the observations made on the locomotor capabilities of several animal species with a special emphasis on cats and including primates and man after complete spinal lesions. We show that animals can perform well-coordinated walking movements of the hindlimbs when they are placed on a treadmill belt and this locomotion is also adaptable to speed and perturbations. Cats with partial spinal lesions of the ventral and ventrolateral parts of the cord can perform voluntary quadrupedal locomotion overground or on the treadmill albeit with deficits in weight support and interlimb coordination. We also show that some drugs such as clonidine (an alpha-2 noradrenergic agonist) can be used to trigger locomotion in early-spinal cats and discuss the effects of various neurotransmitter systems on the expression of the locomotor pattern in both complete and partial spinal cats. It is concluded that a pharmacological approach could be used, in combination with other ap...

Integrative and Comparative Biology, Feb 1, 2004
SYNOPSIS. This paper reviews some aspects of locomotor plasticity after spinalisation and after p... more SYNOPSIS. This paper reviews some aspects of locomotor plasticity after spinalisation and after peripheral nerve lesions. Adult cats can recover spontaneous hindlimb locomotion on a treadmill several days or weeks after a complete section of the spinal cord at T13. The kinematics as well as the electromyographic activity are compared in the same animal before and after the spinal section to highlight the resemblance of locomotor characteristics in the two conditions. To study further the mechanisms of spinal plasticity potentially underlying such locomotor recovery, we also summarize the locomotor adaptation of cats submitted to various types of peripheral nerve section of either ankle flexor or extensor muscles or after denervation of the hindpaws' cutaneous inputs. It is argued that, even in the spinal state, cats have the ability to compensate for such lesions of the peripheral nervous system suggesting that the spinal cord has a significant potential for adaptive plasticity that could be used in rehabilitation strategies to restore locomotion after spinal cord injury.

Brain Research, Apr 1, 1999
This study investigated the effects of antidromically conducted nerve impulses on the transmissio... more This study investigated the effects of antidromically conducted nerve impulses on the transmission of orthodromic volleys in primary Ž. Ž. afferents of the hindlimb in decerebrated paralyzed cats. Two protocols were used: A Single skin and muscle afferents N s 20 isolated Ž. from the distal part of cut dorsal rootlets L7-S1 were recorded while stimulation was applied more caudally. The results showed that during the trains of three to 20 stimuli, the orthodromic firing frequency decreased or ceased, depending on the frequency of stimulation. Ž. Remarkably, subsequent to these trains, the occurrence of orthodromic spikes could be delayed for hundreds of ms 15r20 afferents and Ž. sometimes stopped for several seconds 10r20 afferents. Longer stimulation trains, simulating antidromic bursts reported during Ž. locomotion, caused a progressive decrease, and a slow recovery of, orthodromic firing frequency 7r20 afferents , indicating a Ž. cumulative long-lasting depressing effect from successive bursts. B Identified stretch-sensitive muscle afferents were recorded intra-axonally and antidromic spikes were evoked by the injection of square pulses of current through the micropipette. In this case, one to three antidromic spikes were sufficient to delay the occurrence of the next orthodromic spike by more than one control inter-spike interval. If the control inter-spike interval was decreased by stretching the muscle, the delay evoked by antidromic spikes decreased proportionally. Overall, these findings suggest that antidromic activity could alter the mechanisms underlying spike generation in peripheral sensory receptors and modify the orthodromic discharges of afferents during locomotion.
Annals of the New York Academy of Sciences, Nov 1, 1998
Annals of the New York Academy of Sciences, Nov 1, 1998
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Papers by Serge Rossignol