Modelling spinal circuitry involved in locomotor pattern generation: insights from the effects of afferent stimulation

A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-centre rhythm generator (RG) and pattern formation (PF) networks has been developed from observations obtained during fictive locomotion in decerebrate cats. Sensory afferents have been incorporated in the model to study the effects of afferent stimulation on locomotor phase switching and step cycle period and on the firing patterns of flexor and extensor motoneurones. Here we show that this CPG structure can be integrated with reflex circuits to reproduce the reorganization of group I reflex pathways occurring during locomotion. During the extensor phase of fictive locomotion, activation of extensor muscle group I afferents increases extensor motoneurone activity and prolongs the extensor phase. This extensor phase prolongation may occur with or without a resetting of the locomotor cycle, which (according to the model) depends on the degree to which sensory input affects the RG and PF circuits, respectively. The same stimulation delivered during flexion produces a temporary resetting to extension without changing the timing of following locomotor cycles. The model reproduces this behaviour by suggesting that this sensory input influences the PF network without affecting the RG. The model also suggests that the different effects of flexor muscle nerve afferent stimulation observed experimentally (phase prolongation versus resetting) result from opposing influences of flexor group I and II afferents on the PF and RG circuits controlling the activity of flexor and extensor motoneurones. The results of modelling provide insights into proprioceptive control of locomotion.     

Flexor reflex afferents reset the step cycle during fictive locomotion in the cat

 The generation of locomotor-like spinal rhythms has been proposed to involve two neural centres with mutual reciprocal inhibition (Graham Brown’s ”half-centre” hypothesis). Much later a particular set of segmental flexor reflex pathways were described as being organized in accordance with this half-centre hypothesis. As these pathways became operative following injection of monoaminoxidase inhibitors and l-3,4-dihydroxyphenylalanine (l-dopa), i.e. under the same conditions under which a spontaneous locomotor activity may develop, it was assumed that these particular pathways and spinal rhythm generators involve the same neuronal networks. In order to give further evidence to this hypothesis, we investigated whether short trains to ”flexor reflex afferents” (FRA) reset the spinal locomotor rhythm, i.e. shorten or lengthen the stimulated cycle after which the regular rhythm is resumed with step cycles of the original duration. The experiments were performed in anaemically decapitated, high-spinal curarized cats. A steady locomotor rhythm was induced by injection of nialamide and l-dopa and the influence of electrical stimulation (trains of 50–1000 ms) of FRA (joint, cutaneous, and group II and III muscle afferents) onto this rhythm was tested. Stimulation of FRA induced a clear resetting of the locomotor rhythm, which was mainly characterized by a flexion reflex pattern: during the extension phase the extensor activity was interrupted and a flexion phase was initiated; during the late flexion phase mainly a prolongation of that phase with a variable change of the following extension phase was induced. In addition to this prevailing pattern, stimulation of some nerves (in particular nerves to more distal extensors and the sural nerve) could often prolong extension, when stimulated during the late extension, or terminate the flexor burst and initiate a new extension phase, when stimulated during the late flexion phase. This pattern is probably due to the concomitant stimulation of group I afferents in the case of the muscle nerves and to separate non-FRA pathways in the case of the sural nerve. The results demonstrate that the interneurones of the FRA pathways, which are operative during l-dopa-induced locomotion in spinal animals, can be considered as neuronal elements of the rhythm-generating network for locomotion. Received: 25 June 1996 / Accepted: 27 April 1998     

Proprioceptive input resets central locomotor rhythm in the spinal cat

Summary The reflex regulation of stepping is an important factor in adapting the step cycle to changes in the environment. The present experiments have examined the influence of muscle proprioceptors on centrally generated rhythmic locomotor activity in decerebrate unanesthetized cats with a spinal transection at Th12. Fictive locomotion, recorded as alternating activity in hindlimb flexor and extensor nerves, was induced by administration of nialamide (a monoamine oxidase inhibitor) and L-DOPA. Brief electrical stimulation of group I afferents from knee and ankle extensors were effective in resetting fictive locomotion in a coordinated fashion. An extensor group I volley delivered during a flexor burst would abruptly terminate the flexor activity and initiate an extensor burst. The same stimulus given during an extensor burst prolonged the extensor activity while delaying the appearance of the following flexor burst. Intracellular recordings from motoneurones revealed that these actions were mediated at premotoneuronal levels resulting from a distribution of inhibition to centres generating flexor bursts and excitation of centres generating extensor bursts. These results indicate that extensor group I afferents have access to central rhythm generators and suggest that this may be of importance in the reflex regulation of stepping. Experiments utilizing natural stimulation of muscle receptors demonstrate that the group I input to the rhythm generators arises mainly from Golgi tendon organ Ib afferents. Thus an increased load of limb extensors during the stance phase would enhance and prolong extensor activity while simultaneously delaying the transition to the swing phase of the step cycle.     

Stimulation of the group I extensor afferents prolongs the stance phase in walking cats

Group I afferents in nerves innervating the lateral gastrocnemius-soleus (LG-Sol), plantaris (P1), and vastus lateralis/intermedius (VL/VI) muscles were stimulated during walking in decerebrate cats. The stimulus trains were triggered at a fixed delay following the onset of bursts in the medial gastrocnemius muscle. Stimulation of all three nerves with long stimulus trains (>600 ms) prolonged the extensor bursts and delayed the onset of flexor burst activity. LG-Sol nerve stimulation had the strongest effect; often delaying the onset of flexor burst activity until the stimulus train was ended. By contrast, flexor bursts were usually initiated before the end of the stimulus train to the P1 and VL/VI nerves. The minimum stimulus strength required to increase the cycle period was between 1.3×threshold and 1.6×threshold for all three nerves. Simultaneous stimulation of the P1 and VL/VI nerves produced a larger effect on the cycle period than stimulation of either nerve alone. The spatial summation of inputs from knee and ankle muscles suggests that the excitatory action of the group I afferents during the stance phase is distributed to all leg extensor muscles. Stimulation of the group I afferents in extensor nerves generally produced an increase in the amplitude of the heteronymous extensor EMG towards the end of the stance phase. This increase in amplitude occurred even though there were only weak monosynaptic connections between the stimulated afferents and the motoneurones that innervated these heteronymous muscles. This suggests that the excitation was produced via oligosynaptic projections onto the extensor motoneuronal pool. Stimulation with 300 ms trains during the early part of flexion resulted in abrupt termination of the swing phase and reinitiation of the stance phase of the step cycle. The swing phase resumed coincidently with the stimulus offset. Usually, stimulation of two extensor nerves at group I strengths was required to elicit this effect. We were unable to establish the relative contributions of input from the group 1a and group 1b afferents to prolonging the stance phase. However, we consider it likely that group Ib afferents contribute significantly, since their activation has been shown to prolong extensor burst activity in reduced spinal preparations. Thus, our results add support to the hypothesis that unloading of the hindlimb during late stance is a necessary condition for the initiation of the swing phase in walking animals.     

Entrainment of the locomotor rhythm by group Ib afferents from ankle extensor muscles in spinal cats

Summary 1. Previous studies have concluded that the timing of the locomotor rhythm can be strongly influenced by input from group Ib afferents from leg extensor muscles (Duysens and Pearson 1980; Conway et al. 1987). The main objective of the present study was to obtain additional evidence for this conclusion by examining the characteristics of entrainment of the locomotor rhythm by rhythmic stimulation of group I afferents and by rhythmic force pulses in the ankle extensor muscles. 2. A reduced, non-immobilized preparation was developed in spinal cats that allowed isometric contractions of ankle extensor muscles to be elicited by ventral root stimulation during the expression of locomotor activity. The same preparation was used to examine the influence of electrically stimulating group I afferents from the ankle extensors and the effect of rhythmically stretching these muscles. The locomotor rhythm was initiated by sustained mechanical stimulation of the perineum following the administration of Clonidine and, in some preparations, Naloxone. 3. The timing of the onset of flexor burst activity was examined during entrainment with saw-tooth and ramp-and-hold stretches of the ankle extensor muscles. Flexor bursts were initiated about 200 ms following the release from the stretch, and this latency was independent of the entrainment frequency. 4. The locomotor rhythm was readily entrained by rhythmic contractions of the ankle extensor muscles produced by ventral root stimulation provided the magnitude of the contractions was greater than about 10N. Repetitive stimulation of group I muscle afferents from the ankle extensors also entrained the locomotor rhythm, with the timing of motor activity being similar to that during entrainment with rhythmic muscle contractions. Burst activity in the ipsilateral extensors was coincident with the stimulus trains in both cases. This similarity argues for entrainment being produced mainly by input from group Ib afferents. 5. The functional implication of the results of this and previous studies is that input from group Ib afferents during the stance phase of walking acts to inhibit generation of flexor burst activity and to promote extensor activity. The proposal that a decline in Ib activity near the end of the stance phase is involved in regulating the stance to swing transition is discussed.CRSN, Physiologie, Faculte de Medecine, C.P. 6128, succursal A, Montréal, Quebec, Canada, H3C 3J7     

Parallel reflex pathways from flexor muscle afferents evoking resetting and flexion enhancement during fictive locomotion and scratch in the cat

Reflex actions of muscle afferents in hindlimb flexor nerves were examined on ipsilateral motoneurone activity recorded in peripheral nerves during midbrain stimulation-evoked fictive locomotion and during fictive scratch in decerebrate cats. Trains of stimuli (15–30 shocks at 200 Hz) were delivered during the flexion phase at intensities sufficient to activate both group I and II afferents (5 times threshold, T ). In many preparations tibialis anterior (TA) nerve stimulation terminated ongoing flexion and reset the locomotor cycle to extension (19/31 experiments) while extensor digitorum longus (EDL) stimulation increased and prolonged the ongoing flexor phase activity (20/33 preparations). The effects of sartorius, iliopsoas and peroneus longus muscle afferent stimulation were qualitatively similar to those of EDL nerve. Resetting to extension was seen only with higher intensity stimulation (5 T ) while ongoing flexor activity was often enhanced at group I intensity (2 T ) stimulation. The effects of flexor nerve stimulation were qualitatively similar during fictive scratch. Reflex reversals were consistently observed in some fictive locomotor preparations. In those cases, EDL stimulation produced a resetting to extension and TA stimulation prolonged the ongoing flexion phase. Occasionally reflex reversals occurred spontaneously during only one of several stimulus presentations. The variable and opposite actions of flexor afferents on the locomotor step cycle indicate the existence of parallel spinal reflex pathways. A hypothetical organization of reflex pathways from flexor muscle afferents to the spinal pattern generator networks with competing actions of group I and group II afferents on the flexor and extensor portions of this central circuitry is proposed.     

Transmission in a locomotor-related group Ib pathway from hindlimb extensor muscles in the cat

It has been previously shown that phasic stimulation of group I afferents from ankle and knee extensor muscles may entrain and/or reset the intrinsic locomotor rhythm; these afferents are thus acting on motoneurones through the spinal rhythm generators. It was also concluded that the major part of these effects originates from Golgi tendon organ Ib afferents. Transmission in this pathway to lumbar motoneurones has now been investigated during fictive locomotion in spinal cats injected with nialamide and l-DOPA, and in decerebrate cats with stimulation of the mesencephalic locomotor region. In spinal cats injected with nialamide and l-DOPA, it was possible to evoke long-latency, long-lasting reflexes upon stimulation of high threshold afferents before spontaneous fictive locomotion commenced. During that period, stimulation of ankle and knee extensor group I afferents evoked oligosynaptic excitation of extensor motoneurones, rather than the classical Ib inhibition. Furthermore, a premotoneuronal convergence (spatial facilitation) between this group I excitation and the crossed extensor reflex was established. During fictive locomotion, in both preparations, the transmission in these group I pathways was phasically modulated within the step cycle. During the flexor phase, the group I input cut the depolarised (active) phase in flexor motoneurones and evoked EPSPs in extensor motoneurones; during the extensor phase, the group I input evoked smaller EPSPs in extensor motoneurones and had virtually no effect on flexor motoneurones. The above results suggest that the group I input from extensor muscles is transmitted through the spinal rhythm generator and more particularly, through the extensor half-centre. The locomotor-related group I excitation had a central latency of 3.5–4.0 ms. The excitation from ankle extensors to ankle extensors remained after a spinal transection at the caudal part of L6 segment; the interneurones must therefore be located in the L7 and S1 spinal segments. Candidate interneurones for mediating these actions were recorded extracellularly in lamina VII of the 7th lumbar segment. Responses to different peripheral nerve stimulation (high threshold afferents and group I afferents bilaterally) were in concordance with the convergence studies in motoneurones. The interneurones were rhythmically active in the appropriate phases of the fictive locomotor cycle, as predicted by their response patterns. The synaptic input to, and the projection of these candidate interneurones must be fully identified before their possible role as components of the spinal locomotor network can be evaluated.     

Reflexes induced by nerve stimulation in walking cats with implanted cuff electrodes

Summary Neural cuffs, implanted around various hindlimb nerves (sural, common peroneal, posterior tibial), were used to deliver brief stimulus trains to unrestrained cats walking on a treadmill. The resulting perturbations of the step cycle were evaluated by analyzing the EMG bursts recorded from the ankle extensors and by high speed cinematography. It was found that relatively weak stimulation (1.4 to 2 X T) of the posterior tibial nerve was very effective in eliciting a prolongation of the flexion phase provided the stimuli were applied just prior to the expected onset of the ankle extensor EMG burst. This ipsilateral hyperflexion was correlated with a prolongation of the contralateral extension. The same stimuli applied during stance usually evoked a yielding of the stimulated leg and a prolongation of the ongoing contralateral stance. In addition to these flexor and extensor reflex effects, it was found that low threshold stimulation of the sural and common peroneal nerves resulted in a powerful reflex activation of the ankle extensors. In contrast, stimulation of the gastrocnemius-soleus nerve (a muscle nerve) produced no discernible behavioral effects, even for stimuli at 3 X T, indicating that the observed reflexes are probably mediated by cutaneous afferents. The results were largely confirmed in experiments using the same cuffs implanted in spontaneously walking premammillary cats.     

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)     

Supraspinal and segmental signals can be transmitted through separate spinal cord pathways to enhance locomotor activity in extensor muscles in the cat

 The fine control of locomotion results from a complex interaction between descending signals from supraspinal structures and sensory feedback from the limbs. In this report, we studied the interaction between vestibulospinal volleys descending from Deiters’ nucleus and group I afferent input from extensor muscles. It has been shown that both pathways can exert powerful control over the amplitude and the timing of muscle bursting activity in the different phases of the step cycle. The effects of stimulating these pathways on the fictive locomotor rhythm were compared in decerebrate, partially spinal cats (ipsilateral ventral quadrant intact) injected with nialamide and l-dopa. As reported before, stimulation of both Deiters’ nucleus and group I fibres from ankle extensor muscles, when given during the flexor phase, stopped the flexor activity and initiated activity in extensors. When applied during the extensor phase, the same stimulation prolonged the extensor activity and therefore delayed the onset of flexor activity. This similarity suggests that the two pathways might converge on common spinal interneurones. This possibility was tested with the spatial facilitation technique in lumbosacral motoneurones. Deiters’ nucleus and group I fibres from extensor muscles were stimulated with different intensities and with several different coupling intervals. Motoneurones showing clear di- and/or polysynaptic excitation from both pathways were retained for analysis. Surprisingly, in all cases, there were no signs of spatial facilitation, but a simple algebraic sum of the two excitatory postsynaptic potentials. This result indicates that each input acts on the rhythm generator through separate interneuronal pathways. Received: 20 August 1996 / Accepted: 14 November 1996     

Neural mechanisms underlying the clasp-knife reflex in the cat. I. Characteristics of the reflex

1. The goal of this study was to characterize the clasp-knife reflex by the use of stretch and isometric contraction of ankle extensor and flexor muscles in decerebrated cats with bilateral dorsal hemisections of their spinal cords at segment T12. 2. Stretch of an extensor muscle evoked inhibition in both homonymous and synergistic extensor muscles. The similarities between homonymous and synergistic inhibition suggest that similar neural mechanisms were responsible. 3. Homonymous and synergistic clasp-knife inhibition showed several characteristic features: 1) inhibition was evoked only by large stretches that produced significant muscle force. Short stretches that did not produce large forces evoked only excitation; 2) the magnitude of clasp-knife inhibition increased with increasing initial motor output, as reflected in the level of rectified EMG; 3) the time course of reflex inhibition evoked by ramp-and-hold stretch was characterized by segmentation of EMG during ramp stretch, dynamic overshoot of inhibition at the end-of-ramp stretch, and slow but usually complete decay of inhibition during maintained stretch; 4) inhibition persisted beyond the termination of stretch, and 5) inhibition showed adaptation to repeated stretch. 4. Isometric contraction of the soleus or medial gastrocnemius, produced by electrical stimulation of the muscle nerve, also evoked powerful synergistic-reflex inhibition via similar mechanisms as stretch-evoked, clasp-knife inhibition. Stretch evoked a greater degree of inhibition than did contraction, indicating that receptors responsive to both stretch and contraction contribute to clasp-knife inhibition. 5. The reflex effects produced by stretching the soleus or medial gastrocnemius were not confined to the homonymous and close synergistic muscles. Extensor muscles were inhibited and flexor muscles were excited throughout the hindlimb, which paralleled the pattern of a flexion-withdrawal reflex evoked by cutaneous stimulation. 6. Stretch of a flexor muscle, the tibialis anterior, evoked the same spatial pattern and time course of reflex action as stretch of an extensor muscle--inhibition of extensor muscles and excitation of flexor muscles throughout the hindlimb, including homonymous excitation of the tibialis anterior. 7. We conclude that neither Golgi tendon organs nor secondary spindle afferents are likely to contribute significantly to clasp-knife inhibition because their responses to stretch and isometric contraction differ from the reflex actions evoked by stretch and contraction.(ABSTRACT TRUNCATED AT 400 WORDS)     

A kinematic and electromyographic study of cutaneous reflexes evoked from the forelimb of unrestrained walking cats

A kinematic and electromyographic (EMG) analysis was undertaken of the responses evoked in the forelimb of the cat by either mechanical obstruction of the forelimb during the swing phase of locomotion or by electrical stimulation of low-threshold cutaneous afferents during both swing and stance. Mechanical obstruction of the forelimb with a stiff metal rod evoked a complex response that allowed the cat to smoothly negotiate the obstacle without undue disruption of the overall locomotor rhythm. The initial movements were a flexion of the shoulder, together with a locking of the elbow joint, and a dorsiflexion of the wrist, which caused the limb to withdraw from the obstacle. They were followed by an extension of the shoulder, a flexion of the elbow, and a ventroflexion of the wrist, which together brought the limb forward and above the obstacle. The associated and complex pattern of short- and long-latency EMG responses was shown to be related to different aspects of the movement. At the shoulder there was a strong activation of flexor muscles; these responses were of long duration (greater than or equal to 100 ms) and generally lasted throughout the period of shoulder flexion. At the elbow, both flexor and extensor muscles were activated at short latency (9-13 ms). In flexors, this was followed by a cessation and subsequently an augmentation and prolongation of their activity. Dorsiflexors of both the wrist and digits were activated at short latency (10-12 ms) and remained active throughout the period of dorsiflexion of these joints. An injection of a local anesthetic into the area of skin contacted by the metal rod reduced or abolished all of the reflex responses, which suggests that the integrity of cutaneous reflex pathways is essential for the elaboration of these responses. Electrical stimulation of a cutaneous nerve innervating the distal forelimb (the superficial radial nerve) resulted in qualitatively similar, although weaker, responses to those obtained with the mechanical stimulation. Terminal experiments confirmed that these responses were mediated by low-threshold cutaneous afferents. Electrical stimulation also evoked short-latency excitatory responses (10-12 ms) in extensor muscles of the elbow. Generally, the largest reflex effects were obtained during the period of swing for flexor, extensor, and bifunctional muscles. During stance the stimulus was normally ineffective in exciting flexor muscles and in extensors evoked a short-latency inhibition, which was frequently followed by an increase in activity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Facilitation of transmission via inhibitory pathway 1a to spinal extensor motoneurons in response to stimulation of the forelimb nerves in cats

Activation of forelimb flexor reflex afferent in cats anesthetized with a mixture of Chloralose and Nembutal evoked temporospatial facilitation in the reciprocal inhibitory pathways to spinal extensor motoneurons. The amplitude of disynaptic reciprocal 1a inhibitory postsynaptic potentials (IPSP) evoked in the extensor motoneurons by activation of the most excitable fibers of the nerve supplying the antagonist muscle increased several-fold using conditioning stimulation of the forelimb nerve. Facilitation of 1a IPSP occurred on a background of IPSP evoked by descending inter-limb discharges. Facilitation of 1a IPSP had a latent period of 18–20 msec and could last to 60 msec. The possible role of inhibitory 1a interneurons in interlimb coordination is discussed. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 3, pp. 430–435, March, 1999.     

Gender-specific knee extensor torque,flexor torque,and muscle fatigue responses during maximal effort contractions

The purpose of this study was to examine gender differences in knee extensor and flexor peak torque, work, power, and muscle fatigue during maximal effort isokinetic contractions. Subjects included 19 healthy male and 20 healthy female volunteers. Following a dynamic warm-up period, subjects performed 30 reciprocal, concentric maximal knee extension and flexion contractions at a pre-set angular velocity of 3.14 rad·s^–1 on the Biodex Isokinetic Dynamometer. Values for knee extensor peak torque, work, and power were calculated for each repetition over an angular displacement of 1.05 rad for each repetition. The single highest repetition value for knee extensor and flexor peak torque, work, and power was then calculated relative to body mass (N·m·kg^–1, J·kg^–1, W·kg^–1) and allometric-scaled (N·m·kg^{– n} , J·kg^{– n} , W·kg^{– n} ) units. The allometric-scaled units were derived from a log–log transformation and linear regression analysis to calculate the exponent to which body mass is raised. The rate of quadriceps femoris muscle fatigue was calculated as the decline in each isokinetic variable by the linear slope from the single highest repetition value through the 30th repetition, and by two different fatigue indexes. The results demonstrate higher knee extension and flexion peak torque, work, and power in absolute, relative, and allometric-scaled units for males compared to females. Males exhibited higher fatigue rates for both muscle groups of each isokinetic variable than females, as described by the slope and the fatigue index, except when adjusted for peak values via analysis of covariance. The findings suggest that during maximal-effort muscle contractions, males exhibit a higher susceptibility to muscle fatigue than females, a phenomenon that may be related to an inherent ability to generate higher knee extensor and flexor torque. Electronic Publication     

Convergence on Interneurones Mediating the Reciprocal Ia Inhibition of Motoneurones

Interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as “Ia inhibitory interneurones”) were recorded in the lumbar spinal cord of the cat. Volleys in ipsilateral and contralateral high threshold muscle afferents, cutaneous afferents and high threshold joint afferents evoked a mixture of polysynaptic excitation and inhibition. These effects were ascribed to pathways activated by flexor reflex afferents (FRA) and in addition a specific ipsilateral low threshold cutaneous pathway. Ia inhibitory interneurones excited monosynaptically from flexor nerves received stronger net excitation by volleys in ipsilateral FRA than did extensor coupled interneurones, while the opposite pattern was seen from the contralateral FRA. These patterns are similar to those found in flexor and extensor motoneurones respectively. The FRA inhibition in Ia inhibitory interneurones was partly mediated by “opposite” Ia inhibitory interneurones, i.e. those which are mediating the Ia inhibition of la inhibitory interneurones. The extent to which the FRA inhibition is transmitted by Ia inhibitory interneurones was roughly estimated by its susceptibility to recurrent depression by antidromic ventral root stimulation. The main conclusion is that most segmental pathways seem to evoke their effects in parallel to motoneurones and Ia inhibitory interneurones which are monosynaptically linked to the same muscle. The functional importance of this conclusion is discussed in a following report.     

Characterization of hindlimb muscle afferents involved in ventilatory effects observed in decerebrate and spinal preparations

Summary Neurogenic changes of phrenic activity have previously been observed during periodic passive motions of one hindlimb in decorticate, unanaesthetized and curarized rabbit preparations before and after high spinal transection (Palisses et al. 1988). In decerebrate and spinal preparations, we aimed to determine, through rhythmic electrical stimulation of hindlimb muscle nerves, which muscle afferents are involved in these effects. In decerebrate preparations, these electrical stimulations (trains of shocks at 80 Hz for 300 ms every second for 20 s) produced ventilatory effects when group I+II afferent fibres of either flexor or extensor nerves were stimulated together and more powerful changes as soon as group III fibres were recruited. Stimulation of group I fibres alone induced no such effects. When present, these changes in respiratory activity consisted of a maintained decrease of the respiratory period due to both inspiratory and expiratory time shortening; in addition, the amplitude of the phrenic bursts greatly increased at the onset of electrical stimulation. After spinal transection at C2 level and pharmacological activation by nialamide and DOPA, only short-lasting phrenic bursts developed spontaneously; the electrical stimulation of group II and mainly group III flexor afferent fibres induced large amplitude phrenic activity whereas the stimulation of the same extensor afferents was relatively ineffective. The activation of phrenic motoneurones during group III flexor afferent stimulation was closely linked to each 300 ms period of stimulation. While the phrenic effects obtained in the spinal preparations by natural and by electrical periodic stimulation are quite similar to each other, those produced in decerebrate preparations differ substantially. It is concluded that the regulation of phrenic activity in decerebrate and spinal rabbit preparations by hindlimb proprioceptive afferents involves different muscle receptors; perhaps joint proprioceptors for the medullary resetting and muscle receptors connected to group III afferent fibres for the spinal reflex activation of phrenic motoneurones.     

A fast propriospinal inhibitory pathway from forelimb afferents to motoneurones of hindlimb flexor digitorum longus

In high spinalized cats the propriospinal effects of forelimb afferents upon 145 motoneurones of seven different flexor and extensor hindlimb muscles were investigated with intracellular recording. All types of motoneurones showed late (latency longer than 6 msec) excitatory or mixed excitatory-inhibitory effects to forelimb nerve stimulation. Only in flexor digitorum and hallucis longus (FDL) motoneurones were distinct effects with shorter latencies observed, which, however, were exclusively inhibitory. The IPSPs were evoked from cutaneous and muscle afferents and had a minimal central latency of 3.1 msec. They were probably mediated via a trisynaptic pathway.     

The role of cutaneous afferents from the distal hindlimb in the regulation of the step cycle of thalamic cats

Summary The pad and the plantar surface of the foot were stimulated electrically in thalamic cats. Weak stimulation evoked an extensor reflex in the animal at rest. The same stimuli in a spontaneously walking animal applied during the stance phase produced an increase both in amplitude and duration of the ongoing extensor activity. When given during the swing phase, the stimuli either prolonged the ongoing flexor activity and/or shortened the following extensor burst. These changes in flexor and extensor burst duration were reflected in changes in the step cycle duration.Similar results were seen with direct stimulation of the sural nerve. For the latter experiments the ipsilateral hindlimb was fixed and denervated except for the ankle extensors and flexors, which showed rhythmic contractions correlated normally with the walking movements of the three remaining limbs. At rest, threshold stimulation of the sural nerve evoked a reflex contraction in the triceps surae of the fixed leg. The same stimuli applied during the contraction phase of the fixed triceps surae during walking resulted in a larger and longer extensor contraction and a delay of the following flexion. Stimulation during the relaxation phase of the fixed triceps surae reduced the duration of the following contraction phase. The findings are discussed in relation to the possible role of cutaneous input during locomotion.     

Effects of an NMDA-receptor antagonist,MK-801, on central locomotor programming in the rabbit

Summary NMDA has been shown to disclose spinal fictive locomotor activity in various in vitro preparations. In the present work the NMDA-mediated effects of endogenously released excitatory aminoacids (EAA) on fictive locomotion in the adult rabbit preparation were assessed in vivo using systemic injections of a non competitive NMDA-antagonist, MK-801. In acute low spinal and curarized preparations, the amplitude of the spontaneous fictive locomotor activities recorded from hindlimb muscle nerves after nialamide-DOPA pretreatment was much decreased in flexor and extensor nerves after MK-801 administration (0.25 mg/kg i.v.) whereas the locomotor period increased slightly. The more potent locomotor bursts, evoked by repetitive sural nerve stimulation at 10 Hz during 10 s, were differently affected after MK-801: the main effect was a lengthening of the locomotor period and a less drastic drop in the burst amplitude. These changes in the burst period were maximal for activities evoked by A fibre group stimulation (+100%) and less when C fibres were recruited (+70%). In decerebrate curarized preparations where the locomotor sequences were evoked either by sural nerve stimulation or by stimulation of the mesencephalic locomotor region, MK-801 (0.25 mg/kg i.v.) caused the same drop in burst amplitude (by at least 50%) as in the spinal preparation but, in constrast, it reinforced rhythmic bursting: this was revealed by a clear shortening (up to-65%) of the locomotor period and by the prolongation of rhythmic bursting after stimulation. All these effects obtained in decerebrate preparations were maximal 20–30 min after MK-801 injection. Among the spinal reflexes tested by dorsal root stimulation, the mono- and disynaptic reflexes were unaffected by MK-801; the effect was limited to flexor and extensor polysynaptic reflexes which were depressed. With regard to the lumbar locomotion generators, the interpretation of the above results leads us to propose three levels of NMDA-mediated controls of locomotion by endogenously released EAA: two frequency modulations respectively responsible for the activation of the spinal locomotion generator by group A cutaneous afferents and for the strong supraspinal depression of this spinal generator; finally an amplitude modulation, achieved at a spinal, probably interneuronal level, that can amplify the out-puts of the rhythmic generated signals without modifying the pattern.     

Convergence onto interneurons subserving primary afferent depolarization of group I afferents

The aim of the study was to investigate whether common or independent neuronal pathways are used to evoke primary afferent depolarization (PAD) from selectively activated group Ia and Ib afferents of different muscles. To this end, the spatial facilitation of effects of various afferents, indicating convergence on the same interneurons, was used as a test. Its occurrence was assessed on dorsal root potentials (DRPs) evoked in unspecified fibers or using intra-axonal recording from identified group Ia muscle spindle afferents or group Ib tendon organ afferents. Spatial facilitation has been found in PAD pathways a) from various Ia-afferents, whether of flexors or extensors; b) from various Ib-afferents, whether of flexors or extensors; and c) from flexor Ib-afferents and flexor or extensor Ia-afferents. In contrast, no indications have been found for common pathways from extensor Ib- and any Ia-afferents under conditions that proved effective in other combinations. Latencies of those components of PAD that appeared as a result of the spatial facilitation ranged from 2 to more than 7 ms, indicating that the convergence occurred in the shortest (trisynaptic) as well as longer pathways. The same patterns of convergence have been found in PAD pathways to extensor and flexor Ia-afferents (in experiments with intraaxonal recording from these afferents). The possibility might thus be considered that some neuronal pathways are used to modulate transmission via Ia-afferents independently of their muscle origin. The same might hold true for extensor and flexor Ib-afferents. Generally, it is concluded that the minimal number of distinct neuronal populations subserving PAD of group I afferents may be two to six. Additionally, actions of cutaneous, joint, and interosseous afferents on DRPs from Ia-afferents were reexamined to further the comparison between neurons mediating PAD and those mediating postsynaptic excitation or inhibition of motoneurons. Only depression of Ia DRPs followed stimulation of these afferents at intensities of 1.5-2.0 times threshold and higher; lower threshold afferents were apparently ineffective. On the basis of lack of convergence of extensor Ib and Ia muscle afferents and of low-threshold cutaneous afferents, interneurons mediating PAD may thus be distinguished from the interneurons subserving Ib and Ia-like-Ib postsynaptic actions in motoneurons. The latter are coexcited by these three groups of afferents.