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S Rossignol

Publications and source records attributed to S Rossignol.

At least 19 recordsLinked to original sources
PubMed2007

Characteristics and mechanisms of locomotion induced by intraspinal microstimulation and dorsal root stimulation in spinal cats.

Intraspinal microstimulation (ISMS) through a single microelectrode can induce locomotion in cats spinalized at T(13) 1 wk before (untrained) or after 3-5 wk of treadmill training. Here we study the optimal parameters of ISMS and the characteristics of locomotion evoked. ISMS was applied in the dorsal region of segments L(3)-S(1) at different lateralities (midline to 2.5 mm) and after an intravenous injection of clonidine (noradrenergic agonist). Kinematics and electromyographic recordings were used to characterize locomotion. ISMS could induce a bilateral locomotor pattern similar to that obtained with perineal stimulation, and the characteristics of locomotion varied according to the spinal segment stimulated. Mechanisms by which ISMS could evoke locomotion were then investigated by stimulating, inactivating, or lesioning different spinal structures. Dorsal root stimulation (DRS), just like ISMS, could evoke a variety of ipsi- and bilateral nonlocomotor movements as well as locomotor responses. This suggests that sensory afferent pathways are involved in the production of locomotion by ISMS. Microinjections of yohimbine (noradrenergic antagonist) in L(3) and L(4) segments or a complete second spinal lesion at L(3)-L(4) abolished all locomotor activity evoked by ISMS applied at more caudal segments. Progressive dorsoventral spinal lesions at L(3) or L(4) and restricted ventral lesions at L(4) further suggest that the integrity of the ventral or ventrolateral funiculi as well as the L(3)-L(4) segments are critical for the induction of locomotion by ISMS at L(5) to S(1) or by DRS at these caudal segments.

Adrenergic alpha-Antagonists↗
PubMed2006

The epigenetic imprinting defect of patients with Beckwith-Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region.

BACKGROUND: Genomic imprinting refers to an epigenetic marking resulting in monoallelic gene expression and has a critical role in fetal development. Various imprinting diseases have recently been reported in humans and animals born after the use of assisted reproductive technology (ART). All the epimutations implicated involve a loss of methylation of the maternal allele (demethylation of KvDMR1/KCNQ1OT1 in Beckwith-Wiedemann syndrome (BWS), demethylation of SNRPN in Angelman syndrome and demethylation of DMR2/IGF2R in large offspring syndrome), suggesting that ART impairs the acquisition or maintenance of methylation marks on maternal imprinted genes. However, it is unknown whether this epigenetic imprinting error is random or restricted to a specific imprinted domain. AIM: To analyse the methylation status of various imprinted genes (IGF2R gene at 6q26, PEG1/MEST at 7q32, KCNQ1OT1 and H19 at 11p15.5, and SNRPN at 15q11-13) in 40 patients with BWS showing a loss of methylation at KCNQ1OT1 (11 patients with BWS born after the use of ART and 29 patients with BWS conceived naturally). RESULTS: 3 of the 11 (27%) patients conceived using ART and 7 of the 29 (24%) patients conceived normally displayed an abnormal methylation at a locus other than KCNQ1OT1. CONCLUSIONS: Some patients with BWS show abnormal methylation at loci other than the 11p15 region, and the involvement of other loci is not restricted to patients with BWS born after ART was used. Moreover, the mosaic distribution of epimutations suggests that imprinting is lost after fertilisation owing to a failure to maintain methylation marks during pre-implantation development.

Autoantigens↗
PubMed2006

Silver-Russell syndrome and its genetic origins.

Silver-Russell syndrome (SRS) is both clinically and genetically a heterogeneous congenital disorder. Patients are characterised by severe intrauterine and post-natal growth retardation, dysmorphic facial features and, asymmetry. Various chromosome abnormalities have been associated with the disease, involving most often chromosome 7 and 17. In about 7% of sporadic cases, maternal uniparental disomy of chromosome 7 has been detected. Most recent findings suggest that imprinting defects within the 11p15 region also play a role in SRS.

Abnormalities, Multiple↗
PubMed2005

Mid-lumbar segments are needed for the expression of locomotion in chronic spinal cats.

In acute experiments performed in decerebrated and spinalized (T13) cats, an intraspinal injection of clonidine, a noradrenergic agonist, restricted to mid-lumbar segments L3-L4, can induce hindlimb locomotion, whereas yohimbine, a noradrenergic antagonist, can block spinal locomotion, and a second spinal lesion at L4 can abolish all locomotor activity. In the present study, we investigated whether the abolition of locomotion after this second spinal lesion was due to an acute spinal shock or to the functional disconnection of the rostral and caudal lumbar segments. In seven cats, first spinalized at T13 and having recovered treadmill locomotion, a second transection was performed at lower lumbar levels. Video and electromyographic recordings were used to evaluate locomotor performance. Results show that after a second transection at L2 or rostral L3 levels, spinal locomotion was maintained; when the second lesion was performed at caudal L3 or L4, all locomotor activity was abolished even after several weeks of attempted locomotor training; vigorous fast paw shakes (FPS) were observed in all cases; and after an intraperitoneal injection of clonidine in cats with a second transection below L4, perineal stimulation induced hyperextension of the hindlimbs but no locomotion. Considering that the main motoneuron pools of the hindlimbs are caudal to L4 and are still functional after the second spinal transection, as evidenced by the presence of FPS, we conclude that the mid-lumbar spinal segments are essential for the specific expression of spinal locomotion but not necessarily for other rhythmic motor patterns.

Adrenergic alpha-Agonists↗
PubMed2003

Contribution of cutaneous inputs from the hindpaw to the control of locomotion. I. Intact cats.

The goal of this study was to evaluate the role of hindpaw cutaneous feedback in the control of locomotion, by cutting some (in one cat) or all (in 2 cats) cutaneous nerves bilaterally at ankle level. Kinematic and electromyographic (EMG) recordings were obtained before and for several weeks after denervation during level and incline (15 degrees up and down) treadmill walking. Ladder walking and ground reaction forces were also documented sporadically. Early after the denervation (1-3 days), cats could not walk across a ladder, although deficits were small during level treadmill walking. Increased knee flexion velocity caused a 14% reduction in swing phase duration. EMG activity was consistently increased in knee, ankle, and toe flexors, and in at least one knee or ankle extensor. The adaptive changes during walking on the incline were much reduced after denervation. Ladder walking gradually recovered within 3-7 wk. By this time, level treadmill walking kinematics had completely returned to normal, but EMG activity in flexors remained above control. Incline walking improved but did not return to normal. Mediolateral ground reaction forces during overground walking were increased by 200%. It is concluded that in intact cats, cutaneous inputs contribute more to demanding situations such as walking on a ladder or on inclines than to level walking. Active adaptive mechanisms are likely involved given that the EMG locomotor pattern never returned to control level. The companion paper shows on the other hand that when the same cats are spinalized, these cutaneous inputs become critical for foot placement during locomotion.

Animals↗
PubMed2003

Contribution of cutaneous inputs from the hindpaw to the control of locomotion. II. Spinal cats.

The goal of these experiments was to define the contribution of hindpaw cutaneous inputs in the expression of spinal locomotion in cats. In 3 cats, some (n = 1) or all (n = 2) cutaneous nerves were cut bilaterally at ankle level before spinalization. This denervation caused small deficits that were gradually compensated as reported in the companion study. After spinalization, the completely denervated cats never recovered plantar foot placement or weight bearing of the hindquarters despite more than 35 days of treadmill training. Although normal electromyographic rhythmic activity developed at the hip and knee, ankle flexors and extensors were abnormally coactivated during stance. In contrast, the partially denervated cat regained foot placement and weight support 15 days after spinalization. However, after completing the denervation, foot placement and weight bearing were lost as in previous cats. In a 4th cat, spinalization was performed before denervation and the cutaneous nerves were cut sequentially in the right hindlimb only. Rapid locomotor adaptation occurred after cutting the deep peroneal, saphenous, and sural nerves. Later, cutting the superficial peroneal nerve produced paw drag, which was compensated within 8 days. On cutting the last cutaneous nerve (tibial), plantar foot placement was lost despite another 71 days of training. On the one hand, these experiments show that some cutaneous inputs are necessary for appropriate plantar foot placement and weight bearing of the hindquarters during spinal locomotion and, on the other hand, that locomotor compensation to partial cutaneous denervation after spinalization reveals important adaptive capacities of the spinal cord.

Adrenergic alpha-Agonists↗
PubMed2002

Recovery of locomotion in the cat following spinal cord lesions.

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

Animals↗
PubMed2001

Pharmacological aids to locomotor training after spinal injury in the cat.

This Topical Review summarizes some of the work we have done mainly in the cat using agonists and antagonists of various neurotransmitter systems injected intravenously or intrathecally to initiate or modulate the expression of hindlimb locomotion after a spinal lesion at T13. The effects of the same drugs are compared in various preparations: complete spinal, partial spinal or intact cats. This has revealed that there can be major differences in these effects. In turn, this suggests that although the locomotor rhythm might normally be triggered and modulated by the activation of a variety of receptors (noradrenaline, serotonin, glutamate), after spinalization there appears to be a predominance of glutamatergic mechanisms. Recent work also suggests that, in the cat, the integrity of the midlumbar segments is crucial for the expression of spinal locomotion. Taken together, this work raises some hope that a targeted pharmacotherapy with better understood drugs and mode and locus of delivery could become a clinical reality.

2-Amino-5-phosphonovalerate↗
PubMed2001

Adaptive locomotor plasticity in chronic spinal cats after ankle extensors neurectomy.

After lateral gastrocnemius-soleus (LGS) nerve section in intact cats, a rapid locomotor compensation involving synergistic muscles occurs and is accompanied by spinal reflex changes. Only some of these changes are maintained after acute spinalization, indicating the involvement of descending pathways in functional recovery. Here, we address whether the development of these adaptive changes is dependent on descending pathways. The left LGS nerve was cut in three chronic spinal cats. Combined kinematics and electromyographic (EMG) recordings were obtained before and for 8 d after the neurectomy. An increased yield at the ankle was present early after neurectomy and, as in nonspinal cats, was gradually reduced within 8 d. Compensation involved transient changes in step cycle structure and a longer term increase in postcontact medial gastrocnemius (MG) EMG activity. Precontact MG EMG only increased in one of three cats. In a terminal experiment, the influence of group I afferents from MG and LGS on stance duration was measured in two cats. LGS effectiveness at increasing stance duration was largely decreased in both cats. MG effectiveness was only slightly changed: increased in one cat and decreased in another. In cat 3, the plantaris nerve was cut after LGS recovery. The recovery time courses from both neurectomies were similar (p > 0.8), suggesting that this spinal compensation is likely a generalizable adaptive strategy. From a functional perspective, the spinal cord therefore must be considered capable of adaptive locomotor plasticity after motor nerve lesions. This finding is of prime importance to the understanding of functional plasticity after spinal injury.

Adaptation, Physiological↗
PubMed2001

Comparison of the effect of intrathecal administration of clonidine and yohimbine on the locomotion of intact and spinal cats.

Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate "fictive" locomotion in immobilized acutely spinalized cats and alpha(2)-noradrenergic agonists, such as 2,6,-dichloro-N-2-imidazolidinylid-enebenzenamine (clonidine), can induce treadmill locomotion soon after spinalization. However, the activation of noradrenergic receptors may be not essential for the basic locomotor rhythmicity because chronic spinal cats can walk with the hindlimbs on a treadmill in the absence of noradrenergic stimulation because the descending pathways are completely severed. This suggests that locomotion, in intact and spinal conditions, is probably expressed and controlled through different neurotransmitter mechanisms. To test this hypothesis, we compared the effect of the alpha(2) agonist, clonidine, and the antagonist (16 alpha, 17 alpha)-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L(3)--L(4) before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50-150 microg/100 microl) modulated the locomotor pattern slightly causing a decrease in duration of the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustained hind limb locomotion in the first week after the spinalization at a time when the cats were paraplegic. Later, after the spontaneous recovery of a stable locomotor pattern, clonidine prolonged the cycle duration, increased the amplitude and duration of flexor and extensor bursts, and augmented the foot drag at the onset of swing. In intact cats, yohimbine at high doses (800--1600 microg/100 microl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 microg/100 microl), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spinalization, yohimbine had no effect even at the largest doses. These results indicate that, in the intact state, noradrenergic mechanisms probably play an important role in the control of locomotion since blocking the receptors results in a marked disruption of walking. In the spinal state, although the receptors are still present and functional since they can be activated by clonidine, they are seemingly not critical for the spontaneous expression of spinal locomotion since their blockade by yohimbine does not impair spinal locomotion. It is postulated therefore that the expression of spinal locomotion must depend on the activation of other types of receptors, probably related to excitatory amino acids.

Adrenergic alpha-Agonists↗
PubMed2000

Initiating or blocking locomotion in spinal cats by applying noradrenergic drugs to restricted lumbar spinal segments.

After an acute low thoracic spinal transection (T13), cats can be made to walk with the hindlimbs on a treadmill with clonidine, an alpha2-noradrenergic agonist. Because previous studies of neonatal rat spinal cord in vitro suggest that the most important lumbar segments for rhythmogenesis are L1-L2, we investigated the role of various lumbar segments in the initiation of walking movements on a treadmill of adult cats spinalized (T13), 5-6 d earlier. The locomotor activities were evaluated from electromyographic and video recordings. The results show that: (1) localized topical application of clonidine in restricted baths over either the L3-L4 or the L5-L7 segments was sufficient to induce walking movements. Yohimbine, an alpha2-noradrenergic antagonist, could block this locomotion when applied over L3-L4 or L5-L7; (2) microinjections of clonidine in one or two lumbar segments from L3 to L5 could also induce locomotion; (3) after an intravenous injection of clonidine, locomotion was blocked by microinjections of yohimbine in segments L3, L4, or L5 but not if the injection was in L6; (4) locomotion was also blocked in all cases by additional spinal transections at L3 or L4. These results show that it is possible to initiate walking in the adult spinal cat with a pharmacological stimulation of a restricted number of lumbar segments and also that the integrity of the L3-L4 segments is necessary to sustain the locomotor activity.

Adrenergic alpha-Agonists↗
PubMed2000

Activation of locomotion in adult chronic spinal rats is achieved by transplantation of embryonic raphe cells reinnervating a precise lumbar level.

Traumatic lesions of the spinal cord yield a loss of supraspinal control of voluntary locomotor activity, although the spinal cord contains the necessary circuitry to generate the basic locomotor pattern. In spinal rats, this network, known as central pattern generator (CPG), was shown to be sensitive to serotonergic pharmacological stimulation. In previous works we have shown that embryonic raphe cells transplanted into the sublesional cord of adult rats can reinnervate specific targets, restore the lesion-induced increase in receptor densities of neurotransmitters, promote hindlimb weight support, and trigger a locomotor activity on a treadmill without any other pharmacological treatment or training. With the aim of discriminating whether the action of serotonin on CPG is associated to a specific level of the cord, we have transplanted embryonic raphe cells at two different levels of the sublesional cord (T9 and T11) and then performed analysis of the kinematic and EMG activity synchronously recorded during locomotion. Locomotor performances were correlated to the reinnervated level of the cord and compared to that of intact and transected nontransplanted animals. The movements expressed by T11 transplanted animals correspond to a well defined locomotor pattern comparable to that of the intact animals. On the contrary, T9 transplanted animals developed limited and disorganized movements as those of nontransplanted animals. The correlation of the locomotor performances with the level of reinnervation of the spinal cord suggests that serotonergic reinnervation of the L1-L2 level constitutes a key element in the genesis of this locomotor rhythmic activity. This is the first in vivo demonstration that transplanted embryonic raphe cells reinnervating a specific level of the cord activate a locomotor behavior.

Animals↗
PubMed2000

Locomotion and its recovery after spinal injury.

Recent advances indicate not only that the spinal cord has great potential for locomotor recovery after lesion but also that locomotor training can optimise this recovery through some form of 'learning'. Improvement of residual function can also be achieved through the use of various drugs and treatments such as spinal grafts. In spinal-cord-injured humans, a number of recent studies have allowed an objective quantification of the improvement of locomotion through various forms of training and stimulation.

Animals↗
PubMed1999

Antidromic discharges in dorsal roots of decerebrate cats. I. Studies at rest and during fictive locomotion.

Spontaneous rhythmic antidromic discharges have previously been recorded in proximal stumps of cut dorsal roots during locomotion (real and fictive). The goals of the present study were to elucidate (1) whether both orthodromic and antidromic discharges occur in the same dorsal root filament and (2) whether orthodromic discharges have an influence upon antidromic discharges of units in the same filament. Unitary activity was recorded in 70 uncut dorsal root filaments (L6-S1) in 15 decerebrate cats using bipolar Ag/AgCl electrodes. Spikes with similar wave shapes were considered to represent the activity of single units. Spike-triggered averaging (STA), local anaesthesia and transection of filaments were used to determine the direction of propagation of spikes. Spikes with different initial electrical polarities were found in most of the filaments and shown to propagate in opposite directions at rest and during fictive locomotion. On average, there were 38%+/-S.D. 23% antidromically discharging units per filament and their mean conduction velocity was 55 m/s+/-S.D. 25 m/s. After blocking orthodromic activity of the whole filament by a transection or local anesthesia applied distally to the recording site, changes were seen in the antidromic discharges of some units suggesting that spontaneous orthodromic discharges normally seen in the filament may influence the antidromic discharges of some units. Moreover, out of 27 antidromic units recorded during fictive locomotion, 12 were rhythmically modulated with peak discharges occurring in various parts of the locomotor cycle. We conclude that, in uncut dorsal roots, there is a normal coexistence of spontaneous orthodromic and antidromic discharges revealed by STA and that there is an interaction between spontaneous orthodromic and antidromic discharges.

Action Potentials↗
PubMed1999

The effects of antidromic discharges on orthodromic firing of primary afferents in the cat.

This study investigated the effects of antidromically conducted nerve impulses on the transmission of orthodromic volleys in primary afferents of the hindlimb in decerebrated paralyzed cats. Two protocols were used: (A) Single skin and muscle afferents (N=20) isolated 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. Remarkably, subsequent to these trains, the occurrence of orthodromic spikes could be delayed for hundreds of ms (15/20 afferents) and sometimes stopped for several seconds (10/20 afferents). Longer stimulation trains, simulating antidromic bursts reported during locomotion, caused a progressive decrease, and a slow recovery of, orthodromic firing frequency (7/20 afferents), indicating a 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.

Action Potentials↗
PubMed1999

Autoradiographic study of alpha1- and alpha2-noradrenergic and serotonin1A receptors in the spinal cord of normal and chronically transected cats.

Serotoninergic and noradrenergic drugs have been shown to initiate and/or modulate locomotion in cats after spinal cord transection and in patients suffering from spinal cord injuries. To establish a firmer basis for locomotor pharmacotherapy, the distribution of alpha1- and alpha2-noradrenergic and serotonin1A (5-HT1A) receptors was examined in the spinal cord of control cats and of from animals with spinal cord transection at T13 some weeks or months previously. In control cats, the highest levels of alpha1-noradrenergic receptors, labeled with [3H]prazosin, were found in laminae II, IX, and X. The alpha2-noradrenergic receptors, labeled with [3H]idazoxan, were found mainly in laminae II, III, and X, with moderate densities in lamina IX. After spinal transection, both receptors did not change in segments above the lesion. At 15 and 30 days after spinal transection, binding significantly increased in laminae II, III, IV, and X for alpha2 and in laminae I, II, III, and IX for alpha1 receptors in lumbar segments. For longer survival times, binding densities returned to near control values. The 5-HT1A receptors, labeled with [3H] 8-hydroxy-dipropylaminotetralin, were found mainly in laminae I-IV and X. After spinal transection, binding significantly increased only in laminae II, III, and X of lumbar segments at 15 and 30 days. Thereafter, binding returned to control values. The pronounced upregulation of different monoaminergic receptors observed in the lumbar region in the first month after spinal transection suggests that these receptors may be important during the period when cats normally recover functions such as locomotion of the hindlimbs.

8-Hydroxy-2-(di-n-propylamino)tetralin↗