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Biomedical subjects

D Viala

Publications and source records attributed to D Viala.

At least 37 records · Page 2Linked to original sources

Interneurones of the lumbar cord related to spontaneous locomotor activity in the rabbit. I. Rhythmically active interneurones.

In decorticate, unanaesthetized and curarized rabbit preparations displaying spontaneous fictive locomotor sequences, the firing pattern of neurones was recorded extracellularly in the L6-S1 spinal cord. These neurones, located in the intermediate part of the cord, were not invaded by antidromic stimulation of the hindlimb muscle nerves and thus were considered as interneurones (or propriospinal or tract cells ascending to the brain). When compared to the output from the ipsilateral muscle nerves, these neurones were classified as flexor (F INs) or extensor (E INs) according to the phase of the locomotor cycle when they displayed their maximal firing rate. Among 69 F INs, 33 maintained tonic firing during the periods between episodes of locomotor activity. Their maximal firing rate was in phase with the flexor efferent bursts of the locomotor sequence; during the extensor phase, they maintained an instantaneous frequency (i.f.) that was clearly above the resting i.f. Of these neurones, six became completely silent during the initial flexorextensor coactivation that opened the sequence (F1 neurones) whereas the 27 others increased their firing rate at that time (F2 neurones). The other neurones (36 F3) were silent between the locomotor episodes. Although most of them had a rhythmic activity limited to the flexor bursts, some fired throughout locomotor sequence with a maximal rate during flexor bursts. All the 123 E neurones completely stopped firing during the flexor phase. As was the case for F3 neurone firing, E3 neurone firing (34 neurones) occurred only during periods of locomotor activity. Among the neurones that displayed tonic activity between locomotor episodes, the E2 neurones (24 from 123) remained at this resting value during the extensor phase whereas the E1 neurones (65 neurones) showed an increased i.f. for all or part of this phase. These data, which suggest an asymmetrical genesis of the flexor and extensor activities in locomotion, need to be supported by further analysis.

Animals↗

Evidence for the entrainment of breathing by locomotor pattern in human.

In human, it has been shown that interactions between locomotor and respiratory patterns may lead to locomotor-respiratory couplings termed entrainment. In order to prove that this coupling is really an entrainment, we tried to show that it obeys one of the expected rules, i.e. that it evolves and is not present for all imposed locomotor frequencies. For that purpose, seventeen healthy volunteers were asked to run on a treadmill at 14 different locomotor rates (instead of 2 or 3 in previous works) for 40 s. All the subjects did not exhibit the same coupling and different relationships could be obtained: the most commonly observed was 2:1 (2 locomotor activities for a respiratory one) but other forms could appear (4:1 and even 5:2 or 3:2). When the coupling evolution was followed in the same subject, it did not appear for all locomotor frequencies but only for locomotor periods close to harmonics of respiratory ones (absolute coordination). On both sides of these values, it progressively evolved to relative coordination and to the lack of coordination. When two forms of absolute coordination were observed in a same subject, the phase relationships followed the rules of the entrainment. Compared to data obtained in quadrupeds, these results suggest that the entrainment of breathing frequency by the locomotor activity is due to central interactions between the respiratory and locomotor pattern generators and does not depend on a chemical regulation avoided here by short locomotor sequences.

Breathing Exercises↗

Evidence for respiratory interneurones in the C3-C5 cervical spinal cord in the decorticate rabbit.

In mammals, it has long been considered that the bulbo-spinal inspiratory drive provided a direct (monosynaptic) excitation of phrenic motoneurones (Phr Mns). Although such connections have been demonstrated, recent indirect data strongly suggested that the main inspiratory drive is polysynaptic. We tried to directly demonstrate relay respiratory interneurones at the C3-C6 spinal cord level where the Phr Mn pool is located. The experiments were performed on decorticate, unanaesthetized, bilaterally vagotomized and curarized rabbits and the firing pattern of spinal interneurones was compared to the phrenic bursting. Dorsally and dorso-medially to the Phr Mn pool, different classes of inspiratory (54%) and expiratory (46%) interneurones could be identified in the ventral horn. Three classes of inspiratory interneurones were characterized and classified as "I all" (26%), "I late" (43%) and "I tonic" (29%) according to the terminology used by other authors for the bulbospinal inspiratory neurones which drive the spinal respiratory motoneurones. The expiratory interneurones could also be divided into 3 classes: "E all" (48%), "E late" (10%) and "E tonic" (41%). This first direct evidence of inspiratory interneurones at the C3-C6 spinal cord levels can account for the major polysynaptic excitation of the Phr Mns while the presence of numerous expiratory interneurones at this level suggests a polysynaptic bulbo-spinal inhibitory action onto the Phr Mns. These classes of inspiratory and expiratory interneurones did not always coincide with the bulbo-spinal classes of neurones described elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

An attempt to localize the lumbar locomotor generator in the rabbit using 2-deoxy-[14C]glucose autoradiography.

An attempt was made to find the anatomical localization of the lumbar locomotion generators using 2-deoxy-[14C]glucose (2-DG) uptake in acute low spinal preparation of rabbits unanaesthetized, curarized and injected with nialamide and dihydroxyphenylalanine (DOPA). In such conditions, the locomotor generators were forced to work in isolation for 45 min without interruption as attested by the rhythmic activity recorded in hindlimb muscle nerves. Compared to spinal control preparations not activated pharmacologically, the treated animals showed a specific labeling in the intermediate part of the grey matter, extending from L6 to S1.

Action Potentials↗

Evidence for central entrainment of the medullary respiratory pattern by the locomotor pattern in the rabbit.

1) Although periodic passive hindlimb movements can reproduce the enhancement of breathing frequency seen at the onset of muscular exercise, we have shown previously that they were unable to induce the 1:1 coupling which is observed between locomotion and respiration during galloping in quadrupeds. The purpose of this study was to investigate the existence of a central coupling in two experimental situations: first, decorticate - DOPA, and secondly, decerebrate rabbit preparations. 2) After DOPA administration in curarized, vagotomized, decorticate animals, an absolute coordination could be observed between the locomotor bursts (which developed in hindlimb muscle nerves) and phrenic activity. With the temporal evolution of the pharmacological activation, the coupling mode varied from 1:1 to 1:2 during the same experiment with a loss of coordination between these two forms. When the coordination between both motor activities was not produced in such conditions, it could be induced for some imposed frequencies of periodic passive motions applied to the contralateral hindlimb. 3) When the DOPA effects were completely over, a rostro-pontine decerebration allowed locomotor activity to be released and a tight 1:1 coupling could be obtained again between the two motor patterns in this new experimental situation. 4) An analysis of the data revealed that the various forms of coordination obtained in the different experimental situations are due to a central resetting of the respiratory and of the locomotor patterns. The capability of the hindlimb proprioceptive inputs to coordinate locomotor and respiratory patterns in the decorticate-DOPA preparation appeared simply linked to their ability to entrain the activity of the lumbar locomotion generator. It is suggested that these central reciprocal interactions, which have the properties of an entrainment process, are the result of interactions between the lumbar locomotion generator and the medullary respiratory one.

Action Potentials↗

Reflex modulation of phrenic activity through hindlimb passive motion in decorticate and spinal rabbit preparation.

The neurogenic effect of passive hindlimb movement on phrenic nerve discharge was compared in decorticate unanaesthetized and curarized rabbit preparations prior to and after spinal transection. The question of how and where sensory information has access to the central respiratory network was addressed in each case. All passive motions, performed using a mechanical device, were of constant amplitude in a given preparation. The results clearly differed in decorticate and spinal preparations. In the decorticate vagotomized preparation, periodic passive motions led to an immediate shortening of the respiratory period which lasted throughout the periodic stimulation and stopped with its cessation; it did not depend on the frequency of the natural stimulation and was entirely due to a 20% shortening of the expiration time. Maintained full flexion or full extension both induced the same expiration time shortening, but limited to the first two to three respiratory cycles after onset and interruption of stimulation. After spinal transection at the C2 level, and moderate activation with DOPA, no phrenic activity developed in the absence of proprioceptive stimulation. Periodic hindlimb movements evoked simultaneous large bursts in both phrenic nerves during each extension; a 1:1 coordination of phrenic activity with the external imposed period (P) was observed for various P values. A strong phrenic activation could also be elicited through maintained full hindlimb extension but not through full flexion: this activation appeared as rhythmic discharge as long as extension was maintained. It is concluded that proprioceptive inputs act upon the medullary respiration generator and reset its own rhythm whereas, at the spinal level, they elicit an amplitude modulation at phrenic motoneuronal level without acting upon the rate of the spinal "respiration" generator itself; on the same phrenic motoneurons, a subthreshold central activation added to a subthreshold proprioceptive activation probably accounts for the phrenic bursting during maintained extension. Finally, the proprioceptive control from the hindlimb on phrenic activity is processed at different sites of the central respiratory network at medullary and at spinal level, and may depend on different input signals.

Animals↗

Changeover from alternate to synchronous bilateral pattern of the phrenic bursts entrained by fictive locomotion in the spinal rabbit preparation.

Phrenic bursting resulting from locomotor entrainment during fictive locomotion was shown previously in high spinal preparation after nialamide-DOPA administration. The temporal evolution of the bilateral pattern of phrenic vs locomotor activity is considered here. At variance with the bilateral locomotor pattern which is always alternate (fictive stepping), the pattern on both phrenic nerves changes with time after DOPA injection: first alternate, left and right phrenic bursts become synchronous. A study of ipsilateral phrenic-locomotor phase relationships allowed to disclose the way the transition from alternate to synchronous phrenic coupling was achieved: synchronism appeared as resulting from a strong facilitation on the overlapping parts of the bilaterally alternating phrenic bursts; this phase shifting, vs the ipsilateral locomotor pattern, accounts for the transfer of phrenic bilateral coupling.

Action Potentials↗

Different mechanisms involved in supraspinal and spinal reflex regulation of phrenic activity through chest movements.

The coordination of breathing activity with chest movements was compared in the same decorticate rabbit preparations prior to and after a transection at the C2 spinal level. Pharmacological activation was induced with a combination of nialamide and DOPA in the latter situation. The preparation was curarized and chest inflations and deflations were induced by a respirator whose parameters could be modified. In decorticate preparations, phrenic activity was coordinated 1:1 with the respirator period over a large range of imposed periods. Beyond the extreme values a new coupling was achieved with a ratio of either 1:2 or 2:1. Throughout the range of 1:1 coordination, phrenic bursting always happened at a preferred time in the respirator period, although this time differed for the various imposed periods. This coordinated activity required vagal inputs. After spinal transection the phrenic nerves were totally silent; DOPA administration allowed rhythmic activity to develop. In some preparations, phrenic bursts were coordinated 1:1 with the respirator period and remained so for all the imposed periods: the phase of these phrenic discharges relative to the respirator cycle was kept unchanged for the different periods. In addition, there was a modulation of amplitude superimposed on this 1:1 coupling. These spinal phrenic bursts were generally suppressed when the respirator was turned off. From these results, the coordination of phrenic activity with the respirator rate appears to be produced by different mechanisms in the decorticate and in the spinal preparations. In the decorticate animal the periodic vagal inflow reset the activity of the medullary inspiratory generator and entrains it at its own rate. The coordination observed in the spinal preparation results from a periodic peripheral activation of premotoneuronal or motoneural phrenic elements during inflation. If the central bursts provided by the spinal "respiration" generator can fire phrenic motoneurons above threshold, their timing is not dependent on the peripheral inflow; when the motoneurons are fired below threshold by these central inputs, they are probably summing together the central and peripheral excitations, which could account for the amplitude modulation of the coordinated phrenic bursts of pure reflex origin. Possible afferent pathways are discussed.

Action Potentials↗

[Existence of respiratory interneurons in the cervical spinal cord of the rabbit].

A spinal "respiration" generator has been shown to fire phrenic motoneurones in rhythmic bursts. It is very likely driven through bulbo-spinal inspiratory neurones in intact preparations. Although no direct evidence for respiratory interneurones at the C4-C5 spinal levels has been obtained so far (except for Renshaw cells ), it is currently believed that only few inspiratory inputs to the phrenic motoneurones are transmitted monosynaptically from the medulla. We have tried here to record spinal interneuronal respiratory activities in decorticate, unanaesthetized, vagotomized and curarized rabbit preparations. Different functional categories of interneurones could be identified at the C4-C5 spinal levels: inspiratory and expiratory interneurons with various discharge patterns which rather well correspond to the functional categories of inspiratory and expiratory bulbo-spinal neurones described by Bianchi and Richter. In addition, multiunit inspiratory bursting could be followed over several 100 microns during each electrode penetration. The different categories of interneurones were encountered laterally from 700 to 1,000 microns, at depths ranging from 300 to 500 microns dorsally to the phrenic nucleus, down to the nucleus itself. These results indicate that part of the medullary inspiratory drive is channelled via spinal cord interneurones; they also suggest that an inhibition of phrenic motoneurones from the bulbo-spinal expiratory drive takes place via interneurones.

Animals↗

Evidence for direct reciprocal interactions between the central rhythm generators for spinal "respiratory" and locomotor activities in the rabbit.

Rhythm generators for locomotion and respiration have been previously identified in the high spinal rabbit treated with nialamide and DOPA. In curarized preparations, with no sensory feedback, simultaneous recordings of motor commands from the nerves to the diaphragm and to several hindlimb nerves have demonstrated that central (intraspinal) interactions exist between these respiratory and locomotor activities. The purpose of the present study was to investigate the nature of these interactions. Two main possibilities existed: "direct" interactions taking place between the rhythm generators; the activity of one of the rhythm generators modifying the other generator's activity at its "output" (at the interneuronal or motoneuronal level). The present analysis of the timing (and resetting) of activities in the phrenic, hindlimb extensor (gastrocnemius medialis) and flexor (tibialis anterior) nerves suggests a strong direct interaction between the two sets of rhythm generators. Each new locomotor cycle thus only begins at the termination of a "long-lasting phrenic burst" and a respiratory burst can only occur at certain parts of a locomotor cycle.

Afferent Pathways↗

[Mechanisms of locomotion in mammals].

From biochemical studies of the hindlimb locomotor cycle in the cat, it appears that joint angle excursions are more simple at hip than at more distal joints. The pattern of EMG activity for the different hindlimb muscles is not simple but detailed and is roughly kept the same in the deafferented preparation and in the chronic spinal preparation too: these results show the central and spinal origin of the basic rhythm generation of the locomotor pattern. What is added to this basic mechanism by the supraspinal levels is: (1) a tonic activation which is necessary for the locomotor bursting to be initiated and maintained; (2) an adjustment of four limb posture to ensure equilibrium throughout a locomotor episode. The cerebellum is likely a leader in latter control. The basic spinal pattern is also controlled by peripheral feed-back signals which operate at spinal level and can delay the next locomotor cycle as long as the limb is loaded. On the other hand, a gain control of simple spinal reflexes is achieved by the spinal locomotion generator versus the phase of the locomotor cycle.

Animals↗

Evidence for respiratory and locomotor pattern generators in the rabbit cervico-thoracic cord and for their interactions.

In addition to the wellknown fictive locomotion, a fictive respiration can also be obtained in decorticate, unanaesthetized rabbit preparations after curarization and vagotomy. Both patterns were abolished after high spinal (C2 or C3) transection. Spinal rhythmic capabilities could be disclosed after administration of nialamide and DOPA: together with the earlier demonstrated locomotor-like bursting in hindlimb and forelimb muscle nerves, two different types of phrenic bursting patterns could be observed, depending on endtidal CO2 levels: (1) short lasting phrenic bursts (SLPBs), coordinated with locomotor bursts, result of a locomotor driving process; (2) when end-tidal CO2 was slightly increased (4.5 instead of 4.0%), long lasting phrenic bursts (LLPBs) developed: they have no causal link with the locomotor bursts. Intraspinal interactions were shown to operate between these rhythmic patterns: (1) the already mentioned caudo-rostral driving from hindlimb or posterior locomotion generators (pLGs) onto forelimb bursting and onto phrenic activity too (providing SLPBs in the latter case); (2) the rostro-caudal inhibition of fore- and hindlimb locomotor activity throughout each LLPB. Since forelimb locomotor-like bursting and LLPBs could still be obtained after functional isolation of the cervico-thoracic cord (through C2 and Th12 spinal transections) with comparable interactions as before Th12 transection, it is concluded that: two categories of generators, forelimb or anterior locomotion generators (aLGs), and chemosensitive respiration generators (RGs) are both present in this part of the cord, on the one hand; interactions between RGs and pLGs are likely to be achieved via aLGs on the other.

Animals↗

[Demonstration of generators of the locomotor and respiration rhythms in the cervico-thoracic spinal cord of rabbits].

In curarized Rabbits whose cervico-thoracic cord has been isolated through C2 and Th12 transections, a pharmacological activation (nialamide-DOPA) disclosed distinct rhythmic efferent activities, locomotor-like bursts in forelimb muscle nerves and "respiratory" discharges in the phrenic nerves: they originate respectively from a cervico-thoracic locomotion generator and from a "respiration" generator; these spinal generators appear to be interconnected with each other.

Animals↗

Central locomotor programming in the rabbit.

In decorticate, unanaesthetized and curarized rabbit preparations, with both hindlimbs deafferented, locomotor-like discharges were recorded from nerves to flexors and extensors and their time patterns were compared. The bursts of rhythmic activities recorded from nerves to several flexor muscles acting at either joint were shown to be synchronous, with no differences in their time of onset. The same was true for the extensors. Nerves to bifunctional muscles (biceps posterior, semi-tendinosus and tenuissimus) acting on two consecutive joints (knee flexors, hip extensors) could display two consecutive bursts in each locomotor cycle, one being pure flexor and the other an extensor discharge. It is shown here that this functional bivalence is programmed centrally and can be modulated, i.e. the relative importance of the flexor and the extensor bursts can be changed in a predictable way through afferent (proprioceptive or cutaneous) influences, or through activation of the descending monoaminergic pathways. In extreme cases, complete functional reversal was observed in these bifunctional muscle nerves.

Action Potentials↗

Coordinated rhythmic bursting in respiratory and locomotor muscle nerves in the spinal rabbit.

In unanaesthetized, curarized spinal rabbits (C2 level) treated with Niamide and DOPA, rhythmic activities were recorded from the phrenic nerves; close coordination was observed between the phrenic bursts and the locomotor bursts which developed in hindlimb muscle nerves. The frequency of phrenic bursts was reduced after a second spinal transection at the Th12 level, while rhythms in the hindlimb remained unchanged. It thus appears that in the spinal preparation and under certain pharmacological conditions, phrenic bursts generated by the cervico-thoracic spinal cord can be driven by the lumbar generators of locomotion; spinal links thus exist between these hindlimb locomotion generators and spinal interneuronal networks involved in phrenic motoneuronal activation, may be via hindlimb forelimb driving.

Animals↗