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Biomedical subjects

S Rossignol

Publications and source records attributed to S Rossignol.

At least 19 recordsLinked to original sources

Spinal pattern generation.

Recent research in the field of spinal pattern generation has concentrated on three main areas: the effects of various transmitters on spinal rhythmic patterns in reduced preparations (neonatal rats, chick embryos, tadpole embryos, lampreys); the changes in membrane properties of different elements of the generating circuits; and the interactions between central generating mechanisms and afferent inputs. The important message is that new properties of neural membranes, as well as new reflex responses, have been identified that could not have been predicted in the absence of such rhythmic activity.

Afferent Pathways

Enhancement of locomotor recovery following spinal cord injury.

Recent advances have been made in new experimental approaches to enhance locomotor recovery in spinal cord-injured subjects. Research in adult animals whose spinal cords have been transected (spinal animals) has focused particularly on locomotor recovery and the use of pharmacological tools to trigger and modulate the locomotor pattern. This provides a rational basis for the rehabilitation and pharmacotherapy of locomotion in spinal cord-injured patients. Findings in the field of locomotor training, locomotor pharmacotherapy, and functional electrical stimulation are reviewed. It is argued that a combination of the various approaches will provide an optimal base for functional locomotor recovery.

Animals

Microstimulation of the medullary reticular formation during fictive locomotion.

1. The present study was designed to determine the effects of microstimulation of the medullary reticular formation (MRF) on the locomotor activity of the cat in the absence of phasic afferent feedback from the limbs. To this end, both short (33 ms) and long (200 ms) trains of stimuli (trains of 0.2-ms pulses at 330 Hz, 35 microA) were applied at 43 loci in the MRF (P:6-12 mm; L:0.5-1.5 mm), and in 3 loci in the medial longitudinal fasciculus (P7.5, L < 0.5 mm) during fictive locomotion in the decerebrate and paralyzed cat. The locomotor pattern was monitored by recording the activity of representative flexor and extensor muscle nerves from each of the four limbs. 2. Short trains of stimuli evoked transient excitatory and/or inhibitory responses in extensor and flexor nerves of each limb that were incorporated into the locomotor pattern. In the majority of sites, excitatory responses were obtained in the motor nerves to both flexor and extensor muscles of the fore- and hindlimbs. The exception to this rule was the ipsilateral triceps, in which the predominant response was inhibitory. The amplitude of these responses was dependent on the time of the locomotor cycle at which the stimulus was delivered, and it was always maximum during the period of activity of the respective nerve. 3. The shortest latency response in the nerves to different muscles of the forelimb averaged between 5.6 and 7.3 ms; for the hindlimbs the values were between 6.9 and 9.3 ms. 4. Changing the depth at which the stimulation was applied in any one trajectory usually produced changes only in the amplitude of the evoked responses but occasionally also caused a change in the sign of these responses, especially in the most ventral regions of the MRF. 5. At 72% of the loci (31/43), short trains of stimulation also changed the duration of the activity in the recorded nerves. These changes were often (20/31 loci) sufficiently strong to alter the duration of the overall locomotor cycle. If one considers only the largest changes produced at each locus, stimulation during the period of ipsilateral extensor activity produced an average reduction in the ipsilateral locomotor cycle duration of 12.8 +/- 8.8% (mean +/- SD), whereas stimulation when the ipsilateral flexor nerve was active produced an average increase in locomotor cycle duration of 27.1 +/- 20.8%. 6. Long trains of stimuli produced similar but larger effects than the shorter trains and always reset the locomotor rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

[Computerized medical register of venous thromboembolic disease at the Grenoble University Hospital Center: description and evaluation].

The number of vascular exams for venous thromboembolic disease increases dramatically in the vascular medicine unit at the Grenoble University Hospital (France). In order to improve the efficiency and the homogeneity of all the medical staff involved, a computerized register has been created. It automatically provides a letter for the prescriber of the consultation. This database, working on a computer network, has three main functions: office automation (medical folder, report), education, and clinical research. The office automation evaluation is performed after a 6 month experience, comparing 100 medical reports about venous thrombosis assisted by the computer to 100 medical reports written before the installation of the system. The introduction of digitized register is real, still this evaluation has induced some modification in the system in order to be more efficient.

Aged

Low-threshold, short-latency cutaneous reflexes during fictive locomotion in the "semi-chronic" spinal cat.

Low-threshold, short-latency cutaneous reflexes evoked in ipsilateral hindlimb motor nerves were examined during fictive locomotion. Locomotion in 11 anaemically decerebrated spinal animals (1-3 weeks after transection at T13-L1) was induced by administration of clonidine, L-dopa and nialamide; by administration of the latter two drugs only; or by exteroceptive stimulation in the absence of any drugs. The caudal and lateral cutaneous sural, caudal cutaneous femoral, saphenous and superficial peroneal nerves were stimulated at low threshold (1.5-3 T). Pooled results from all combinations of cutaneous nerves stimulated and muscle nerves recorded show that the initial response was excitatory in 40 of 50 triceps surae and 17 of 20 semitendinosus (St) electroneurograms (ENGs). These excitatory responses occurred at latencies that ranged from 5 to 15 ms and tended to be maximal during the motor nerve's active period in the step cycle (i.e. they were modulated in a phase-dependent manner). Only three inhibitory responses (9-12 ms earliest latency) were encountered in total: in two St ENGs of one animal and in one lateral gastrocnemius-soleus ENG of a different animal. In two animals a "second" excitatory response (15-25 ms latency) was sometimes recorded in triceps surae and St nerves and, interestingly, could be modulated out of phase with the early response. Weak short-latency excitatory reflexes were also found in contralateral St ENGs when examined. Finally, among medial gastrocnemius, lateral gastrocnemius and soleus nerves, excitatory responses due to stimulation of any particular cutaneous nerve tended to be modulated similarly but were of consistently different amplitude among the three. This finding, together with the general observation that excitatory reflexes produced by stimulation of a particular cutaneous nerve were modulated similarly in extensors (or flexors) of different animals, suggests that spinal circuits generating locomotion may indeed exert a stereotypic control over interneurons in specific cutaneous reflex pathways to motoneurons. The results are primarily discussed in terms of the existing evidence for short-latency excitatory cutaneous reflexes in extensors in a variety of locomotive and non-locomotive preparations.

Animals

Initiation and modulation of the locomotor pattern in the adult chronic spinal cat by noradrenergic, serotonergic and dopaminergic drugs.

The effects of noradrenergic, serotonergic and dopaminergic drugs, and their interaction were studied in 8 adult spinal cats during the first week following spinalisation and up to 3 months, when the animals had reached a steady state in their locomotor pattern. During the first week, when no episodes of coordinated stepping were observed, injection of the serotonergic precursor (DL-5-HTP) or a dopaminergic agonist (apomorphine) failed to induce locomotion. In contrast, injection of either a noradrenaline precursor (L-DOPA) or an agonist (clonidine) induced locomotion when the hindlimbs were placed on a moving belt. The spinal animal demonstrated a bilateral foot placement on the plantar surface, as well as transient weight support of the hindquarters at a treadmill speed up to 0.80 m/s. The movement pattern and the electromyographic activity resemble those of the intact cat in many aspects. This locomotion-triggering effect of L-DOPA or clonidine was also observed when given after DL-5-HTP or apomorphine. At around 3 months following spinalisation, when the animal showed a stable and regular locomotor pattern, injection of clonidine increased the step cycle duration, resulting in a prolonged flexor and extensor burst duration as the EMG amplitude was unchanged or slightly increased. Injected in the same animal, quipazine, a serotonergic agonist, increased both the duration and the amplitude of flexor and extensor EMGs. In contrast to the serotonergic and the noradrenergic agonists, apomorphine and L-DOPA augmented mainly the flexor activity which could even lead to a sustained flexion when the dose was increased. When combining clonidine to a serotonergic drug, the characteristics of the modulation of the locomotor pattern resulting from each drug were retained. The present results demonstrate that (1) the noradrenergic system is probably the most important system for the initiation of locomotion; (2) the three monoaminergic descending systems (mimicked by the precursor and agonists) can modify rather specifically different aspects of the well established locomotor pattern in the same chronic spinal cat and (3) the effect of monoaminergic drugs are reproducible when given in similar time periods in different chronic spinal cats. The present study provides insight into the role of the noradrenergic, serotonergic and dopaminergic system in the initiation and in the modulation of the locomotion pattern following spinalisation. The above studies also provide a basis to investigate the effects of these drugs in spinal cord-injured patients.

Animals

An intracellular study of muscle primary afferents during fictive locomotion in the cat.

1. Presynaptic activity of identified primary afferents from flexor, extensor, and bifunctional hindlimb muscles was studied with intra-axonal recordings during fictive locomotion. Fictive locomotion appeared spontaneously in decorticate cats (n = 9), with stimulation of the mesencephalic locomotor region (n = 4), and in spinal cats injected with clonidine or nialamide and L-DOPA (n = 4). Representative flexor and extensor muscle nerves, recorded to monitor the locomotor pattern and dorsal rootlets of the sixth and seventh lumbar segments, were recorded simultaneously to monitor dorsal root potentials (DRPs). 2. From responses to muscle stretches and, in some instances, twitch contractions of the parent muscle, 75% of the single units examined were putatively identified as spindle afferents (40/53). On the basis of conduction velocity and stimulation threshold, 73% of these were further classified as group I fibers (29/40), the rest as group II fibers. 3. All units (n = 53 with resting potential more negative than -45 mV) showed fluctuations of their membrane potential (up to 1.5 mV) at the rhythm of the fictive locomotion. Subsequent averaging of these fluctuations over several cycles revealed that 89% of all units displayed a predominant wave of depolarization during the flexor phase, followed by a trough of repolarization. In 79% of the units, there was also a second, usually smaller, depolarization during the extensor phase. The relative size of each wave of depolarization could vary with different episodes of fictive locomotion in the same unit and among various afferents from the same muscle in the same experiment. 4. The firing frequency of some afferents from the ankle flexor tibialis anterior (5/16) and the bifunctional muscle posterior biceps-semitendinosus (4/15) was phasically modulated along the fictive step cycle. The maximum frequency always occurred during the flexor phase, i.e., during the largest depolarization of the unit. Because of the absence of phasic sensory input in the curarized animal, we assume that the phasic discharges were generated within the spinal cord and antidromically propagated. Phasic firing was never encountered in afferents from extensor muscles such as triceps surae (0/15) and vastus lateralis (0/4). 5. The results demonstrate that the pattern of rhythmic depolarization accompanying fictive locomotion is similar for the majority of flexor, extensor, and bifunctional group I (and possibly group II) muscle spindle primary afferents. They further indicate that there is a specific phasic modulation of antidromic firing for some flexor and bifunctional muscle spindle afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Fictive motor patterns in chronic spinal cats.

1. Fictive motor patterns were recorded in hind leg nerves of 10 adult chronic spinal cats (spinalized at T13). Four of these animals had been trained to step with their hind legs on a treadmill (late-spinal animals), whereas the remainder received no training and were examined a short time after spinalization (early-spinal animals). 2. A fictive pattern resembling the locomotor pattern for stepping was evoked in all animals in response to stimulation of the skin of the perineal region. (2-[2,6-Dichloroaniline]-2-imidazoline) hydrochloride (Clonidine) at doses ranging from 100 to 500 micrograms/kg iv facilitated the production of this pattern, particularly in early-spinal animals. 3. The fictive locomotor pattern in late-spinal animals was more complex than that occurring in early-spinal animals. In the latter the pattern consisted of an alternation of activity in flexor and extensor nerves, and changing leg position did not qualitatively alter the pattern, whereas in late-spinal animals the relative durations of the bursts in different flexors were usually not the same, and the pattern of flexor activity was dependent on leg position. 4. Moving the legs from extension to flexion progressively decreased the duration of flexor bursts, increased the cycle period, and decreased the ease with which the pattern could be evoked in both early- and late-spinal animals. 5. 1-beta-3,4-Dihydroxyphenylalanine (DOPA)/Isonocotinic acid 2-[(2-benzylcarbamoyl)ethyl]hydrazide (Nialamide) treatment following Clonidine in early-spinal animals increased the complexity of flexor burst activity. This, and other observations, indicates that DOPA and Clonidine do not have strictly identical actions on the locomotor pattern generator. 6. Stimulation of the paws in late-spinal animals produced two patterns of activity distinctly different from the locomotor pattern. of activity distinctly different from the locomotor pattern. One was a short sequence of high-frequency rhythmic activity (at approximately 8 c/s) in response to gently stimulating one paw with a water jet, and the other was a slow rhythm in flexor nerves in response to squeezing the paw. 7. The main conclusion of this investigation is that three distinctly different fictive motor patterns can be generated in chronic spinal cats depending on the method and site of stimulation. These patterns correspond to three different behaviors (locomotion, paw shake, and rhythmic leg flexion) that can be elicited in behaving chronic spinal cats in response to the same stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Phase-dependent modulation of dorsal root potentials evoked by peripheral nerve stimulation during fictive locomotion in the cat.

To help elucidate the role of presynaptic mechanisms in the control of locomotor movements, the transmission of PAD pathways was investigated by recording dorsal root potentials (DRPs) evoked by electrical stimulation of cutaneous and muscle nerves of both hindlimbs at various phases of the fictive step cycle. Fictive locomotion occurred spontaneously in decorticate cats or by stimulating the mesencephalic locomotor region (MLR) as well as in low spinal cats injected with nialamide and L-DOPA. Evoked DRPs were superimposed on a fluctuating DRP accompanying the fictive locomotor rhythm (locomotor DRP) which typically consisted of two peaks of depolarization per cycle, the largest peak occurring during the flexor phase. The amplitude of evoked DRPs was substantially modulated throughout the locomotor cycle and followed a similar modulation pattern for all stimulated nerves whether ipsilateral (i-) or contralateral (co-). The amplitude of evoked DRPs decreased at the beginning of the flexor phase, dropped to a minimum later in the flexor phase and then increased during the extensor phase where it became maximum. Results were comparable in decorticate and spinal preparations and for L6 and L7 rootlets with cutaneous and muscle nerve stimulation. It is noteworthy that the modulation pattern for a given rootlet was similar for i- and co- stimulation, even though the bilateral locomotor DRPs fluctuate out-of-phase with each other, subjecting the stimulated fibres to opposite presynaptic polarization changes. This suggests that the modulation may depend more on the presynaptic mechanisms of the receiving fibres than on those of the stimulated fibres. These results demonstrate that the transmission in spinal pathways involved in primary afferent depolarization (PAD) is phasically modulated by the activity in the spinal locomotor network. It is further suggested that the presynaptic inhibition associated with PAD evoked by movement-related sensory feedback during real locomotion could be modulated in a similar way.

Animals

Phase-dependent modulation of primary afferent depolarization in single cutaneous primary afferents evoked by peripheral stimulation during fictive locomotion in the cat.

Previous results from our laboratory have shown with intra-axonal recordings that hindfoot cutaneous primary afferents are subjected to rhythmic depolarizations during fictive locomotion (L-PAD) suggesting that cutaneous presynaptic mechanisms are activated by the central locomotor program. In this study, we examined the transmission in pathways responsible for primary afferent depolarizations (PAD) of cutaneous fibres during spontaneous fictive locomotion in decorticate cats and in spinal cats injected with nialamide and L-DOPA. PADs were evoked (E-PADs) by electrical stimulation of peripheral nerves and recorded intra-axonally with micropipettes in identified superficialis peroneal (SP; n = 7) and tibialis posterior (TP; n = 17) cutaneous primary afferents. Results showed that the amplitude of E-PADs, which were superimposed on the L-PAD, was deeply modulated throughout the locomotor cycle; decreasing to reach a minimum during the flexor phase and increasing to a maximum during the extensor phase. The results were not statistically different in fibres of the two nerves and in both types of preparation. The amplitude of E-PADs was always maximum during the extensor phase whether there was a large L-PAD or not during that phase. This suggests that the presynaptic mechanisms activated by central locomotor networks (L-PAD) and those activated by peripheral inputs (E-PAD) may in part be controlled differently. The results thus show that the transmission in PAD pathways activated by cutaneous inputs is phasically modulated by the central pattern generator for locomotion. This strongly suggests that the presynaptic inhibition in cutaneous fibres evoked by the movement-related feedback during real locomotion could be similarly modulated.

Animals

The effects of serotonergic drugs on the locomotor pattern and on cutaneous reflexes of the adult chronic spinal cat.

The effects of serotonergic substances on the locomotor pattern and cutaneous reflexes were studied in 3 adult chronic spinal cats trained for 1-3 months to walk with their hindlimbs on a treadmill. The 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan (5-HTP), and two 5-HT agonists, 5-methoxy-N,N-dimethyltryptamine and quipazine, were found to generally increase the step length and augment the amplitude of hindlimb extensors and flexors as well as axial muscles. Correspondingly, the excursion of the hip, the knee and the ankle joints was increased, mainly in the flexion direction. Cyproheptadine, a 5-HT antagonist, partially or completely antagonised these effects. The threshold current needed to elicit a flexion reflex by stimulating the dorsum of the paw through implanted wires, was lower after the injection of 5-HT agonists than in the immediately preceding control period. Fast paw shaking initiated by dipping the paw in water was unchanged after quipazine and was not abolished by cyproheptadine. In accordance with others, our results suggest that serotonergic drugs may increase the excitability of several types of spinal neurones, including motoneurones, and consequently influence the locomotor pattern as well as the reflex responsiveness. The changes observed with serotonergic agonists were different in many respects from those obtained with noradrenergic agonists and these differences are discussed. This may indicate specific roles for these classes of substances on locomotor function and reflex activity and also provide a basis for further clinical investigations.

5-Hydroxytryptophan

Functional organization within the medullary reticular formation of intact unanesthetized cat. I. Movements evoked by microstimulation.

1. The present article described the various patterns of movement evoked in the limbs and neck by microstimulation (33-ms trains, 330 Hz, 0.2-ms pulses at less than or equal to 35 microA) of the medullary reticular formation (MRF) of seven chronically implanted, unanesthetized, intact cats. Altogether 878 loci were stimulated in 83 penetrations. However, as stimulation in the more lateral regions of the MRF was less effective, the results are based on stimulation in 592 loci made in 56 penetrations at distances of between 0.5 and 2.5 mm lateral to the midline. 2. Of these 592 loci, movement of one or more parts of the body was evoked from a total of 539 (91%) sites. Most of these movements were compound in nature, involving movement of one or more limbs as well as the head. Discrete movements were observed only with respect to the head; limb movements were always accompanied by head movement. In addition, hindlimb movements were always accompanied by forelimb movements, although the inverse was generally not true. 3. The most common effects of the stimulation were as follows: a turning of the head to the ipsilateral side (79% of stimulated sites); flexion of the ipsilateral elbow (41%); and extension of the contralateral elbow (45%). Effects in the hindlimbs were more variable and less frequent, with the majority of the effective loci causing flexion of the ipsilateral knee (9%) together with extension of the contralateral knee (8%). In total, including both flexion and extension, 18% of the stimulated sites caused movement of the ipsilateral hindlimb and 11% of the contralateral hindlimb. 4. Although movements of the head were obtained from the whole extent of the brain stem, movements of the forelimbs showed a dorsoventral organization with flexion of the ipsilateral elbow being evoked from the more dorsal regions of the brain stem, whereas contralateral elbow extension was evoked more frequently from the ventral regions. There was a large area of overlap from which movements of both limbs could be obtained simultaneously. Movements of the hindlimbs were more frequently evoked from central and ventral areas of the brain stem and from the most rostral aspect of the explored region. 5. In examining the combinations of movements evoked by the MRF stimulation, it was found that the most commonly evoked pattern was movement of the head to the stimulated side together with flexion of the ipsilateral forelimb and extension of the contralateral forelimb (26.5% of sites).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Functional organization within the medullary reticular formation of intact unanesthetized cat. II. Electromyographic activity evoked by microstimulation.

1. The present study has examined the detailed organization of the medullary reticular formation (MRF) as revealed by microstimulation (33-ms trains of 0.2-ms duration pulses at 330 Hz and 35 microA or less) in the intact, chronically implanted, unanesthetized cat. Stimulus-locked electromyographic (EMG) responses were recorded from flexors and extensors of each of the four limbs, as well as bilaterally from muscles of the neck and back, during stimulation of the same 592 loci that formed the basis of the preceding article. 2. The thresholds of the responses were different for each group of muscles, with, on the average, the neck muscles being activated at the lowest range of currents, 13.8-16.5 microA; forelimb muscles at 16.9-17.9 microA; back muscles at 25.4-25.7 microA; and hindlimb muscles at 21.1-25.7 microA. 3. Whereas stimulation within the MRF evoked movement of the head only to the stimulated side (preceding article), analysis of the EMG responses showed there was frequently bilateral activation of the neck muscles. Similarly, even though stimulation produced predominantly ipsilateral elbow flexion and contralateral elbow extension, most loci caused cocontraction of antagonistic muscles at these joints. Cocontraction was also frequently observed for the hindlimbs. Reciprocal activation of antagonistic muscles was less frequent but was observed in the ipsilateral forelimb as well as in both hindlimbs; it was never observed in the contralateral forelimb. 4. Although excitatory responses were observed from widespread regions for all of the muscles under study, those regions of the MRF that evoked the strongest responses in each muscle showed a large degree of segregation. Muscles of the ipsilateral forelimb were most strongly activated from the rostrodorsal MRF, whereas muscles of the contralateral forelimb were most strongly effected by stimulation caudoventrally. Muscles of the hindlimbs were more strongly activated from the rostral brain stem, although with some exceptions. Responses in axial muscles were evoked from widespread regions of the brain stem but were concentrated further caudally than were the limb muscles. 5. Excitatory responses were much more prevalent than inhibitory responses and were evoked from all regions of the MRF, including the most caudal and ventral areas. The shortest latency responses in each track were, on the average, as follows: 6.6-8.8 ms for the neck; 11.2-13.4 ms for the forelimbs; 13.8-14.2 ms for the back; and 15.9-17.2 ms for the hindlimbs. Inhibitory responses were also evoked from widely distributed regions, which were intermingled with those loci evoking excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Modulation of activity of spindle afferents recorded in trigeminal mesencephalic nucleus of rabbit during fictive mastication.

1. These experiments were based on the findings that antidromic firing is observed in first-order sensory afferents during fictive locomotion and were designed to test the hypothesis that a similar central modulation of afferent discharge occurs during mastication. To do this, spindle afferents were recorded in the trigeminal mesencephalic nucleus (Mes V) of anesthetized and paralyzed rabbits during fictive mastication. The cortical masticatory area was stimulated to induce mastication, and activity of the XIIth or the Vth nerves were recorded to monitor the masticatory motor rhythm. 2. Although we could find little evidence that antidromic discharges invade the somatic region of this class of sensory afferents, we did discover a previously unrecognized type of modulation of afferent firing. 3. Of 83 slowly adapting muscle spindle afferents, 33 were modulated during fictive mastication. In 28 cases, the modulation consisted of a phasic inhibition, whereas for the remaining units it could be either a phasic excitation (n = 2) or an excitation alternating with an inhibition (n = 3). 4. Rapidly adapting units were also tested when encountered. Tonic or phasic excitation was never observed. The presence of inhibition could not be verified for this population because tonic activity could not be maintained by passive stretch. 5. The main electroneurogram (ENG) burst of the XIIth and Vth cranial nerves occurred during the opening phase of the masticatory cycle, and in all cases where the records were clear (22 out of 33), phasic inhibition of the afferents coincided with the ENG burst. 6. There was no difference in the distributions of the modulated and of the unmodulated units along the length of the Mes V nucleus. 7. Approximately 40% of trigeminal spindle afferent cell bodies have dendrites, and we suggest that these are the ones rhythmically modulated during fictive mastication. The possible role of this modulation is discussed.

Animals

The effects of 4-aminopyridine on the cat spinal cord: rhythmic antidromic discharges recorded from the dorsal roots.

In a previous paper, we have reported that 4-aminopyridine (4-AP, i.v., 10 mg/kg) induces in decerebrate spinal and paralyzed cats, a sustained rhythmic activity (2.5-8.5 Hz) in various muscle nerves. We describe here that similar discharges are recorded from the proximal stump of cut cutaneous nerves. The latter rhythmic activity arises from intense antidromic discharges in the dorsal roots. The rhythmic discharges are recorded from dorsal roots of both spinal cord enlargements as well as from thoracic roots. The rhythmic activity is highly synchronous among adjacent dorsal roots. Bilateral activity is also highly cross-correlated, but may be dissociated by unilateral stimulation of one dorsal root. It is not yet possible to determine the precise site where the antidromic discharges recorded from the dorsal roots are generated. 4-AP could act directly at the terminal level of the primary afferents or could activate interneurons impinging upon the terminals.

4-Aminopyridine

Unitary discharges in dorsal and ventral roots after the administration of 4-aminopyridine in the cat.

The administration of 4-aminopyridine (4-AP) in decerebrate paralyzed cats induces centrifugal rhythmic discharges in both ventral and dorsal roots. This study describes the mode of discharge of individual primary afferents as well as some ventral root fibers. Several patterns of antidromic discharge have been observed in primary afferents after the administration of 4-AP. A large proportion of the units (n = 96; 53%) showed rhythmic bursts of discharge related (n = 41) or not (n = 55) to the ongoing rhythmic activity in the peripheral nerves. Other units (n = 86; 47%) discharged either tonically, sporadically or had no antidromic activity at all. The conduction velocity of the non-bursting units was significantly higher (89.7 +/- 18.4 m/s) than that of the bursting units (70.6 +/- 15.4 m/s; P less than 0.01). Ventral roots showed rhythmic activity although less intense than that of the dorsal roots. As in dorsal roots, some fibers showed a rhythmical pattern of discharge related to the mass activity recorded from whole dorsal roots or peripheral nerves, while other units were not related. It is concluded that bursting activity which occurs in peripheral nerves after the administration of 4-AP is mainly the result of the antidromic activation of medium to small size primary afferent fibers.

4-Aminopyridine

Intra-axonal recordings of cutaneous primary afferents during fictive locomotion in the cat.

1. Cutaneous primary afferents were recorded intracellularly during fictive locomotion in decorticated cats with the goal of improving our understanding of how locomotor networks might centrally control the transmission in cutaneous pathways at a presynaptic level. 2. Identified cutaneous axons from superficialis peroneal nerve (SP) or tibialis posterior nerve (TP) were recorded intracellularly together with the electroneurograms (ENGs) of representative flexor and extensor muscle nerves of the hindlimb as well as dorsal root potential from L6 or L7 (DRP). Fictive locomotion occurred spontaneously after decortication (n = 12) or was induced by stimulation of the mesencephalic locomotor region (MLR) (n = 6). 3. The results revealed that all cutaneous axons (82 units with resting potential greater than 45 mV) showed fluctuations of their membrane potential (greater than or equal to 0.5 mV) at the rhythm of the fictive locomotion. The characteristics of fluctuation patterns, common to all cutaneous units, consisted of two depolarization waves per cycle: one related to the flexor activity, the other related to the extensor activity. The flexor-related depolarization was followed by a sharp trough of membrane repolarization. The extensor-related depolarization usually overlapped partly with the flexor-depolarization of the following cycle. The relative size of each depolarization could vary among different afferents of the same nerve in the same animal. Hence, maximal depolarization could occur in different parts of the locomotor cycle, but, for the majority of units (82%), it occurred during the flexor activity. These results were similar for SP and TP units. 4. Twenty percent of the units were discharging with a constant or irregular frequency. Phasic antidromic discharges related to locomotor ENGs were rarely encountered (5/82 units). 5. Linear regression analysis of the temporal relationships between fluctuations of membrane potential of cutaneous axons and locomotor bursts over several cycles showed that the timing of presynaptic events in cutaneous afferents is related to the events of the locomotor output. However, the same type of analysis showed that the amplitude of axonal depolarizations and the amplitude of flexor and extensor locomotor bursts could vary independently. Tight temporal relationships were also found between the depolarizations recorded in cutaneous units and the fluctuations recorded at the dorsal root level (DRP). 6. Based on the assumption that the locomotor fluctuations of cutaneous membrane potential are mediated through the primary afferent depolarization (PAD) pathways associated with presynaptic inhibition, it is proposed that the central pattern generator for locomotion (CPG) could phasically control the efficacy of transmission of cutaneous pathways at a presynaptic level as part of the locomotor program.

Animals

[Severe Epstein-Barr virus infection in an infant].

A 11 month-old boy, without any informative familial pedigree, was admitted for peritonitis after intestinal perforation, associated with signs of pseudolymphoma and histiocytic activation. He developed later unexplained gastrointestinal bleeding and interstitial pneumonitis, which spontaneously improved. All infectious and immunologic studies were negative. Epstein-Barr Virus was found in throat, lungs and blood, whereas the specific antibodies production was delayed. No abnormality was detected 18 months later, except for a disappearance of vaccinal antibodies.

Humans