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Serge Rossignol

Publications and source records attributed to Serge Rossignol.

13 recordsLinked to original sources

Experiments and models of sensorimotor interactions during locomotion.

During locomotion sensory information from cutaneous and muscle receptors is continuously integrated with the locomotor central pattern generator (CPG) to generate an appropriate motor output to meet the demands of the environment. Sensory signals from peripheral receptors can strongly impact the timing and amplitude of locomotor activity. This sensory information is gated centrally depending on the state of the system (i.e., rest vs. locomotion) but is also modulated according to the phase of a given task. Consequently, if one is to devise biologically relevant walking models it is imperative that these sensorimotor interactions at the spinal level be incorporated into the control system.

Afferent Pathways↗

Plasticity of connections underlying locomotor recovery after central and/or peripheral lesions in the adult mammals.

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.

Aging↗

Nonlocomotor and locomotor hindlimb responses evoked by electrical microstimulation of the lumbar cord in spinalized cats.

As a preliminary step to using intraspinal microstimulation (ISMS) for rehabilitation purposes, the distribution of various types of hindlimb responses evoked by ISMS in spinal cats (T(13)) is described. The responses to ISMS applied through a single electrode was assessed, before and after an intravenous injection of clonidine (noradrenergic agonist), using kinematics and electromyographic recordings in subacute (5-7 days, untrained) or chronic (3-5 wk trained on a treadmill) spinal cats. ISMS was applied in the dorsal, intermediate and ventral areas of segments L(3)-L(7), from midline to 3 mm laterally. Uni- and bilateral non-locomotor responses as well as rhythmical locomotor responses were evoked. In the subacute cats, ipsilateral flexion was elicited in the dorsal region of L(3)-L(7), whereas ipsilateral extension was evoked more ventrally and mainly in the caudal segments. Dorsal stimuli could induce ipsilateral flexion followed by ipsilateral extension. Sites inducing bilateral flexion and bilateral extension were similarly distributed to those evoking ipsilateral flexion and extension in the rostrocaudal axis but were evoked from more medial sites. Ipsilateral flexion with crossed extension was evoked from intermediate and ventral zones of all segments and lateralities. Unilateral ipsilateral locomotion was rarely observed. Contralateral locomotion was more frequent and mainly evoked medially, whereas bilateral locomotion was evoked exclusively from dorsal regions. With some exceptions, those distribution gradients were similar in the four conditions (subacute, chronic, pre- and postclonidine), but the proportion of each response could vary. The distribution of ISMS-evoked responses is discussed as a function of known localization of interneurons and motoneurons.

Adrenergic alpha-Agonists↗

Functional plasticity following spinal cord lesions.

Spinal cord injury results in marked modification and reorganization of several reflex pathways caudal to the injury. The sudden loss or disruption of descending input engenders substantial changes at the level of primary afferents, interneurons, and motoneurons thus dramatically influencing sensorimotor interactions in the spinal cord. As a general rule reflexes are initially depressed following spinal cord injury due to severe reductions in motoneuron excitability but recover and in some instances become exaggerated. It is thought that modified inhibitory connections and/or altered transmission in some of these reflex pathways after spinal injury as well as the recovery and enhancement of membrane properties in motoneurons underlie several symptoms such as spasticity and may explain some characteristics of spinal locomotion observed in spinally transected animals. Indeed, after partial or complete spinal lesions at the last thoracic vertebra cats recover locomotion when the hindlimbs are placed on a treadmill. Although some deficits in spinal locomotion are related to lesion of specific descending motor pathways, other characteristics can also be explained by changes in the excitability of reflex pathways mentioned above. Consequently it may be the case that to reestablish a stable walking pattern that modified afferent inflow to the spinal cord incurred after injury must be normalized to enable a more normal re-expression of locomotor rhythm generating networks. Indeed, recent evidence demonstrates that step training, which has extensively been shown to facilitate and ameliorate locomotor recovery in spinal animals, directly influences transmission in simple reflex pathways after complete spinal lesions.

Animals↗

Dynamic sensorimotor interactions in locomotion.

Locomotion results from intricate dynamic interactions between a central program and feedback mechanisms. The central program relies fundamentally on a genetically determined spinal circuitry (central pattern generator) capable of generating the basic locomotor pattern and on various descending pathways that can trigger, stop, and steer locomotion. The feedback originates from muscles and skin afferents as well as from special senses (vision, audition, vestibular) and dynamically adapts the locomotor pattern to the requirements of the environment. The dynamic interactions are ensured by modulating transmission in locomotor pathways in a state- and phase-dependent manner. For instance, proprioceptive inputs from extensors can, during stance, adjust the timing and amplitude of muscle activities of the limbs to the speed of locomotion but be silenced during the opposite phase of the cycle. Similarly, skin afferents participate predominantly in the correction of limb and foot placement during stance on uneven terrain, but skin stimuli can evoke different types of responses depending on when they occur within the step cycle. Similarly, stimulation of descending pathways may affect the locomotor pattern in only certain phases of the step cycle. Section ii reviews dynamic sensorimotor interactions mainly through spinal pathways. Section iii describes how similar sensory inputs from the spinal or supraspinal levels can modify locomotion through descending pathways. The sensorimotor interactions occur obviously at several levels of the nervous system. Section iv summarizes presynaptic, interneuronal, and motoneuronal mechanisms that are common at these various levels. Together these mechanisms contribute to the continuous dynamic adjustment of sensorimotor interactions, ensuring that the central program and feedback mechanisms are congruous during locomotion.

Animals↗

Antidromic discharges in dorsal roots of decerebrate cats. II: studies during treadmill locomotion.

In a previous companion paper [Brain Res. 846 (1999) 87-105] we have shown that the dorsal root activity of a decerebrate cat is composed of both orthodromic and antidromic discharges as determined by spike triggered averaging (STA). Furthermore we have shown that, during fictive locomotion in decerebrate and paralyzed cats, antidromic discharges peak in different parts of locomotion cycle but mainly in the flexion phase. In the present study, we have recorded unit potentials from dorsal rootlets during treadmill locomotion in order to understand better the role of movement-related feedback in the generation of antidromic potentials. The unitary activity of 92 antidromically discharging units was recorded in proximal stumps of cut dorsal roots, and that of 20 such units was recorded in uncut roots using two bipolar Ag/AgCl electrodes in both cases. The activity of 80% (74/92) units in cut filaments and of 70% (14/20) units in uncut ones was phasewise related to stepping movements. The peaks of activity of different units occurred during different phases of the step cycle both in cut and uncut filaments. In most cases, the peak of activity was superimposed upon a background of sustained discharge. After blocking the orthodromic flow in a filament (local anesthesia or distal section), the antidromic discharges continued to peak during the same phase but the rate of the discharges increased. We conclude that movement-related afferent feedback significantly modulates the antidromic discharges in dorsal roots during treadmill locomotion. We suggest that these antidromic discharges have a role in controlling afferent feedback during movement.

Action Potentials↗

Determinants of locomotor recovery after spinal injury in the cat.

After a spinalization at the most caudal thoracic spinal segment, the cat can recover locomotion of the hindlimbs when they are placed on a moving treadmill. This chapter summarizes some of the determinants of such a dramatic recovery of motor function. Fundamental to this recovery is undoubtedly the genetically based spinal locomotor generator, which provides an essential rhythmicity to spinal motoneurons and hence the musculature. Other factors are also important, however. Sensory feedback is essential for the correct expression of spinal locomotion because spinal cats, devoid of cutaneous feedback from the hindfeet, are incapable of plantar foot placement. The neurochemical environment also adapts to spinalization, i.e., the loss of all modulation by descending monoaminergic pathways. Post-transection spinal rhythmicity then becomes more dependent on glutamatergic mechanisms. Finally, we argue that the mid-lumbar spinal segments evolve to play a crucial role in the elaboration of spinal locomotion as their inactivation abolishes spinal locomotion. In summary, the above findings suggest that the recovery of spinal locomotion is determined by a number of factors, each of which must now be more fully understood in the ever-continuing effort to improve the rehabilitation of spinal-cord-injured subjects.

Animals↗

Critical points in the forelimb fictive locomotor cycle and motor coordination: evidence from the effects of tonic proprioceptive perturbations in the cat.

During locomotion, the limbs of one girdle must remain coordinated in different conditions. To understand the neural mechanisms underlying such coordination, tonic protraction/ retraction of one shoulder or tonic flexion/extension of one elbow was applied during fictive locomotion in high decerebrate and paralyzed cats. We studied bilateral changes in the timing and amplitude characteristics of electroneurographic (ENG) muscle nerve bursts of cleidobrachialis (ClB, elbow flexor and shoulder protractor) and the two heads of triceps (long, TriLo, elbow extensor and shoulder retractor and lateral, TriLa, elbow extensor). Perturbations induced bilateral changes in amplitude and timing of ENG bursts that were anchored on certain critical points in the cycle. These critical points could correspond to morphological characteristics within the bursts or to bilateral onsets or offsets of ENG bursts. For instance, in response to shoulder and elbow perturbations, burst changes occur in relation to a fixed point, labeled point C, occurring at about mid-extensor burst and corresponding to a simultaneous abrupt increase in TriLa amplitude and a decrease in amplitude of contralateral ClB. At a point labeled B, corresponding to about mid-flexor burst, ClB amplitude increases above control with elbow extension or starts decreasing with shoulder protraction. Although cycle reorganization is specific for each type of tonic perturbation, a common feature is that the changes in burst duration are achieved through discrete shifts between consecutive critical points. It is postulated that coordination may be based on a discrete temporal cycle structure along which critical points delimiting burst components are shifted.

Animals↗

Critical points in the forelimb fictive locomotor cycle and motor coordination: effects of phasic retractions and protractions of the shoulder in the cat.

This study investigates the responses to phasic shoulder retractions or protractions given at different times in the fictive locomotor cycle of the forelimbs of decerebrate cats. Generally, the responses in flexor and extensor muscles acting at the shoulder or elbow were bilaterally coordinated according to a negative feedback scheme. Perturbations in the direction of the movements that would have taken place if the animal had not been paralyzed tended to shorten the duration of the burst of activity of the muscles active during that phase and vice versa in the opposite phase. Changes in response patterns took place around critical points corresponding to the critical points B-D described in the companion paper using tonic perturbations of the limb. Past point C, at 58% of the ipsilateral extensor burst, protractions no longer prolonged the burst and no longer delayed onset of the contralateral extensor. At point B, occurring at 41% of the contralateral extensor burst, ipsilateral protractions maximally shortened the ipsilateral flexor phase, advancing ipsilateral extensor onset (point D) to point C of the contralateral extensor burst. During a critical period from the end of the ipsilateral flexor (point D) until the contralateral flexor onset, retractions elicited two alternative responses. Either the contralateral extensor activity was abolished and the contralateral flexor turned on, or it persisted for another cycle. We argue that the critical points found here correspond to critical biomechanical events in real locomotion and may underlie a phase-dependent motor coordination.

Animals↗

Treadmill locomotion in the intact and spinal mouse.

Because the genetic characteristics of several inbred strains of mice are well identified, their use is becoming increasingly popular in spinal cord injury research. In this context, it appears particularly important to document adequately motor patterns, such as locomotion in normal mice, to establish some baseline values of locomotor characteristics. It also seems crucial to determine the extent to which mice can express a locomotor pattern after a complete spinal transection to establish a baseline on which one can evaluate the effects of treatments after spinal injury. Therefore, we have used conventional techniques to document the kinematics of treadmill locomotion in intact mice (n = 11) and in mice with a complete section of the spinal cord at T8 (n = 12). The results show that the kinematics and EMG of adult normal mice can be adequately monitored with such conventional equipment and that mice can re-express hindlimb locomotion within 14 d after spinalization, without any pharmacological treatments. The angular excursions of the hip, knee, and ankle are similar to those of the intact mice, although the joints are sometimes more flexed. After spinal cord transection, out-of-phase alternation between the homologous limbs recovered, whereas the timing between homolateral limbs was completely lost. This remarkable ability of mice to express hindlimb locomotion after a complete spinalization should be taken into account in the evaluation of various procedures aimed at promoting the functional recovery of locomotion after spinal lesions.

Animals↗

Effects of intrathecal glutamatergic drugs on locomotion. II. NMDA and AP-5 in intact and late spinal cats.

In a previous article, we have shown that, in cats, intrathecal injections of N-methyl-D-aspartate (NMDA) in the first few days after spinalization at T13 do not induce locomotion as in many other spinal preparations. This is in contrast to alpha-2 noradrenergic receptor stimulation, which can trigger locomotion at this early stage. However, it is known that spinal cats do recover spontaneous locomotion in the absence of descending noradrenergic pathways and that the spinal pattern generator must then depend on other neurotransmitters still present in the cord such as excitatory amino acids. In the present paper, therefore we look at the effects of intrathecal NMDA, a glutamatergic agonist, and 2-amino-5-phosphonovaleric acid (AP-5), an NMDA receptor blocker, in both intact and late spinal cats. Low doses of NMDA had no major effect on the locomotor pattern in both intact and late spinal cats. Larger doses of NMDA in the chronic spinal cat initially produced an increase in the general excitability followed by more regular locomotion. AP-5 in intact cats caused a decrease in the amplitude of the flexion reflex and induced a bilateral foot drag as well as some decrease in weight support but it did not prevent locomotion. However, in late spinal cats, the same dose of AP-5 blocked locomotion completely. These results indicate that NMDA receptors may be critical for the spontaneous expression of spinal locomotion. It is proposed that the basic locomotor rhythmicity in cats is NMDA-dependent and that normally this glutamatergic mechanism is modulated by other neurotransmitters, such as 5-HT and NA.

2-Amino-5-phosphonovalerate↗

Effects of intrathecal glutamatergic drugs on locomotion I. NMDA in short-term spinal cats.

Excitatory amino acids (EAA) have been reported to induce fictive locomotion in different in vitro and in vivo preparations in a variety of species through their actions on both N-methyl-D-aspartate (NMDA), and non-NMDA receptors. NMDA-induced intrinsic membrane properties such as intrinsic motoneuronal membrane oscillations and plateau potentials have been suggested to play a role in the generation of locomotion. There is, however, no information on the ability of NMDA in triggering spinal locomotion in awake behaving animals. Because most of the previous work on the induction of locomotion has concentrated on monoaminergic drugs, mainly noradrenergic drugs, the aim of this study is to examine the potential of NMDA in initiating locomotion in chronic spinal cats within the first week after spinalization. Five cats chronically implanted with an intrathecal cannula and electromyographic (EMG) electrodes were used. EMG activity synchronized to video images of the hindlimbs were recorded. The results show that during the early posttransection period (within the 1st week postspinalization), NMDA did not trigger robust locomotion as did noradrenergic drugs. The predominant effects of NMDA were a general hyperexcitability reflected by fast tremor, toe fanning, and an increase in small alternating hindlimb movements with no foot placement nor weight support. During the intermediate phase posttransection (6-8 days), when the cats were able to make some rudimentary steps with foot placement, NMDA significantly enhanced the locomotor performance, which lasted for 24-72 h postinjection. NMDA was also found to increase the excitability of the cutaneous reflex transmission only in early spinal cats. One possible hypothesis for the ineffectiveness of NMDA in triggering locomotion in early spinal cats could be attributed to the widespread activation of NMDA receptors on various neuronal elements involved in the transmission of afferent pathways that in turn may interfere with the expression of locomotion. The marked effects of NMDA in intermediate-spinal cats suggest that NMDA receptors play an important role in locomotion perhaps through its role on intrinsic membrane properties of neurons in shaping and amplifying spinal neuronal transmission or by augmenting the sensory afferent inputs. The long-term effects mediated by NMDA receptors have been reported in the literature and may involve mechanisms such as induction of long-term potentiation or interactions with neuropeptides. The effects of NMDA injection in intact cats and long-term chronic spinal cats will be addressed in a forthcoming companion paper.

Animals↗