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.     

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.     

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.     

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

Summary 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 11 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 11 to 12 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 11 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.     

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

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

Rhythmic phrenic,intercostal and sympathetic activity in relation to limb and trunk motor activity in spinal cats

During L-DOPA-induced fictive spinal locomotion rhythmic activities in nerves to internal intercostal and external oblique abdominal muscles and in phrenic and sympathetic nerves were observed which were always coordinated with locomotor activity in forelimb and hindlimb muscle nerves. A periodicity with longer lasting tonic phases could be induced by cutaneous nerve stimulation or asphyxia. This activity was observed in limb motor nerves as well as in respiratory motor and sympathetic nerves. A slow independent activity of the phrenic and intercostal nerves or the sympathetic nerves, which could be related to a normal respiratory rhythm or independent sympathetic rhythms was not observed. The findings indicate that during fictive spinal locomotion the activity of spinal rhythm generators for locomotion also projects onto respiratory and sympathetic spinal neurones.     

Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat

Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high-intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just working regimes of a general spinal motor optimal control system containing the intrinsic model of limb movement dynamics. The consequences of this concept and ways of further research are discussed.     

Convergence of central respiratory and locomotor rhythms onto single neurons of the lateral reticular nucleus

We have analyzed the behavior of neurons of the lateral reticular nucleus (LRN) during fictive respiration and locomotion and found that some LRN neurons have both central respiratory and locomotor rhythms. Experiments were conducted on decrebrate, decerebellate, immobilized, and artificially ventilated cats, with the spinal cord transected at the lower thoracic cord. Fictive respiration and fictive forelimb locomotion were ascertained by monitoring activities from the phrenic nerve and forelimb extensor and flexor nerves, respectively. Fictive locomotion was evoked by electrical stimulation of the mesencephalic locomotor region (MRL) or sometimes occurred spontaneously. During fictive locomotion many LRN neurons fired in certain phases of the locomotion cycle; i.e., with respect to the nerve discharge of the ipsilateral forelimb they fired in either the extensor, flexor, extensor-flexor, or flexor-extensor phase. Firing of some LRN neurons was modulated synchronously with central respiratory rhythm. Neurons with inspiratory activity and those with expiratory activity were both found. More than half of these respiration-related LRN neurons had locomotor rhythm as well. The majority of the three types of LRN neurons, i.e., neurons with only locomotor rhythm, those with only respiratory rhythm, and those with both respiratory and locomotor rhythm, were antidromically activated by electrical stimulation of the ipsilateral inferior cerebellar peduncle. Electrical stimulation of the upper cervical cord showed that these LRN neurons, not only locomotion-related but also respiration-related neurons, received short latency inputs from the spinal cord. The LRN neurons studied were distributed widely in the LRN, relatively densely in the caudal two-thirds of the nucleus. No particular differences were detected between the three types of LRN neurons with respect to their location in the nucleus. These results indicate that the information about central respiratory and locomotor rhythms that is necessary for cerebellar control of the coordination between respiration and locomotion converges, at least partly, at the level of the LRN.     

Heart beat fluctuation during fictive locomotion in decerebrate cats: locomotor-cardiac coupling of central origin

Fictive locomotion was evoked by stimulation of the mesencephalic locomotor region (MLR) in immobilized, vagotomized and decerebrate cats. The coherence between heart beat fluctuation and efferent discharges of the hindlimb nerve was used to evaluate the strength of the coupling between the cardiac and locomotor rhythms during MLR-elicited fictive locomotion. This study demonstrated that there was a locomotor-cardiac coupling of central origin.     

Stimulation of a restricted region in the midline cerebellar white matter evokes coordinated quadrupedal locomotion in the decerebrate cat.

In the reflexively standing acute decerebrate cat, we have previously shown that pulse train microstimulation of the hook bundle of Russel in the midline of the cerebellar white matter, through which crossed fastigiofugal fibers decussate, augments the postural tone of neck, trunk, fore-, and hindlimb extensor muscles. In the present study we examined the possible role of such stimulation in evoking locomotion as the animal is supported by a rubber hammock with its feet contacting the moving surface of a treadmill. We were able to provoke well-coordinated, bilaterally symmetrical, fore- and hindlimb movements, whose cycle time and pattern were controlled by appropriate changes in stimulus intensity and treadmill speed. We carefully and systematically mapped this cerebellar locomotor region (CLR) through repeated dorsoventral penetrations with a glass-coated tungsten microelectrode in a single animal and between animals. We found that the optimal locus for evoking locomotion was centered on the midline, at Horsley-Clarke coordinates H0 and P7.0, and extended over a rostrocaudal and dorsolateral range of approximately 0.5 mm. The lowest effective stimulus intensity at the optimal site was in the range of 5-8 microA. Along penetration tracks to left or right of the midline, effective stimulus intensity increased and evoked locomotor patterns were no longer symmetrical, but rather shifted toward the contralateral limbs. In the same animals, controlled locomotion was evoked by stimulating the mesencephalic locomotor region (MLR). With concomitant stimulation of the optimal sites in the CLR and the MLR, each at subthreshold strength, locomotor movements identical to those seen with suprathreshold stimulation of each site alone were evoked. With concomitant stimulation at suprathreshold strength for each site, locomotion became vigorous, with a shortened cycle time. After making ablative lesions at either the CLR or MLR (unilateral or bilateral), controlled locomotion was still evoked at the prior stimulus strength by stimulating the remaining site. Together, these results demonstrate that selective stimulation of the hook bundle of Russel in the midsagittal plane of the cerebellar white matter evokes "controlled" locomotion identical to that evoked by stimulating the MLR. We have shown that the fastigial nucleus is one of the supraspinal locomotion inducing sites and that it can independently and simultaneously trigger brain stem and spinal locomotor subprograms formerly believed to be the domain of various brain stem regions including the MLR and the subthalamic locomotor region.     

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.     

Intercostal and abdominal respiratory motoneurons in the neonatal rat spinal cord: spatiotemporal organization and responses to limb afferent stimulation

Respiration requires the coordinated rhythmic contractions of diverse muscles to produce ventilatory movements adapted to organismal requirements. During fast locomotion, locomotory and respiratory movements are coordinated to reduce mechanical conflict between these functions. Using semi-isolated and isolated in vitro brain stem-spinal cord preparations from neonatal rats, we have characterized for the first time the respiratory patterns of all spinal intercostal and abdominal motoneurons and explored their functional relationship with limb sensory inputs. Neuroanatomical and electrophysiological procedures were initially used to locate intercostal and abdominal motoneurons in the cord. Intercostal motoneuron somata are distributed rostrocaudally from C₇–T₁₃ segments. Abdominal motoneuron somata lie between T₈ and L₂. In accordance with their soma distributions, inspiratory intercostal motoneurons are recruited in a rostrocaudal sequence during each respiratory cycle. Abdominal motoneurons express expiratory-related discharge that alternates with inspiration. Lesioning experiments confirmed the pontine origin of this expiratory activity, which was abolished by a brain stem transection at the rostral boundary of the VII nucleus, a critical area for respiratory rhythmogenesis. Entrainment of fictive respiratory rhythmicity in intercostal and abdominal motoneurons was elicited by periodic low-threshold dorsal root stimulation at lumbar (L₂) or cervical (C₇) levels. These effects are mediated by direct ascending fibers to the respiratory centers and a combination of long-projection and polysynaptic descending pathways. Therefore the isolated brain stem-spinal cord in vitro generates a complex pattern of respiratory activity in which alternating inspiratory and expiratory discharge occurs in functionally identified spinal motoneuron pools that are in turn targeted by both forelimb and hindlimb somatic afferents to promote locomotor-respiratory coupling.     

Activity of interneurons within the L4 spinal segment of the cat during brainstem-evoked fictive locomotion

Summary Extracellular recordings from interneurons located in the L4 spinal segment were made during fictive locomotion produced by electrical stimulation of the mesencephalic locomotor region (MLR) in the paralysed decerebrate cat. Only interneurons within the L4 segment which received group II input from quadriceps, sartorius or the pretibial flexor muscle afferents and which had axonal projections to motor nuclei in L7 were selected for analysis. During the fictive step cycle two thirds of these interneurons fired action potentials during the time of activity in the ipsilateral hindlimb flexor neurograms. These cells were also less responsive to peripheral input during the extension phase of the fictive locomotion cycle. The remaining one third of the interneurons examined were not rhythmically active during locomotion. The possible contributions of the midlumbar interneurons to motoneuron activity during locomotion are discussed.     

Initiation of Locomotion in Decerebrate Cats by Pulsed Magnetic Fields Projected onto Spinal Cord Segments

The motor effects induced by pulsed magnetic fields (PMF) projected onto the lumbar and cervical spinal cord were studied in decerebrate cats. A magnetic coil (inductor) of diameter 8 cm was positioned 1–2 cm above the surface of the spinal cord. Stimulation of the spinal cord with PMF was performed in two regimes: with single impulses with an intensity of 0.5–1 T and with continuous rhythmic stimulation at a frequency of 1 Hz and an intensity of 0.5 T. Application of single stimuli to the lumbar enlargement evoked reflex responses in the proximal and distal hindlimb muscles. Rhythmic stimulation initiated locomotor activity of the limb on a running treadmill, i.e., activated the neural locomotor network of the spinal cord (stepping movement generator). Magnetic stimulation of the lumbar enlargement evoked coordinated stepping movements of the hindlimbs only. Application of PMF to the cervical enlargement induced coordinated stepping movements of all four limbs, hindlimb movements starting before forelimb movements. After cessation of magnetic stimulation, the limbs completed several further coordinated movement cycles. This is the first report of the triggering of limb stepping movement generators with PMF in decerebrate cats. The results obtained here demonstrate that the neural locomotor networks of the spinal cord can be activated noninvasively and open new perspectives for the clinical use of PMF.     

Fictive locomotion of the forelimb evoked by stimulation of the mesencephalic locomotor region in the decerebrate cat

Fictive locomotion, rhythmic nerve discharges mimicking locomotor activities, of the forelimb was found to be evoked by stimulation of the mesencephalic locomotor region (MLR), as that of the hindlimb, in immobilized decerebrate cats with the lower thoracic cord transected. The effective area for fictive locomotion was highly localized in the dorsolateral portion of the MLR, whereas a locomotor movement on the still belt of the treadmill was elicited from a slightly wider area and that on the moving belt from a further expanded area.     

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.     

Mechanism for activation of locomotor centers in the spinal cord by stimulation of the mesencephalic locomotor region

The synaptic pathways of mesencephalic locomotor region (MLR)-evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) recorded from lumbar motoneurons of unanesthetized decerebrate cats during fictive locomotion were analyzed prior to, during, and after cold block of the medial reticular formation (MedRF) or the low thoracic ventral funiculus (VF). As others have shown, electrical stimulation of the MLR typically evoked short-latency excitatory or mixed excitatory/inhibitory PSPs in flexor and extensor motoneurons. The bulbospinal conduction velocities averaged approximately 88 m/s (range: 62-145 m/s) and segmental latencies for EPSPs ranged from 1.2 to 10.9 ms. The histogram of segmental latencies showed three peaks, suggesting di-, tri-, and polysynaptic linkages. Segmental latencies for IPSPs suggested trisynaptic or polysynaptic transmission. Most EPSPs (69/77) were significantly larger during the depolarized phase of the intracellular locomotor drive potential (LDP), and most IPSPs (35/46) were larger during the corresponding hyperpolarized phase. Bilateral cooling of the MedRF reversibly abolished locomotion of both hindlimbs as measured from the electroneurogram (ENG) activity of muscle nerves and simultaneously abolished or diminished the motoneuron PSPs and LDPs. Unilateral cooling of the VF blocked locomotion ipsilaterally and diminished it contralaterally with concomitant loss or decrease the motoneuron PSPs and LDPs. Relative to the side of motoneuron recording, cooling of the ipsilateral VF sometimes uncovered longer-latency EPSPs, whereas cooling of the contralateral VF abolished longer-latency EPSPs. It is concluded that MLR stimulation activates a pathway that relays in the MedRF and descends bilaterally in the VF to contact spinal interneurons that project to motoneurons. Local segmental pathways that activate or inhibit motoneurons during MLR-evoked fictive locomotion appear to be both ipsilateral and contralateral.     

Effects of Spinal Cord Electrical Stimulation in Patients with Vertebrospinal Pathology

Until now, no scientific neurophysiologic methods of diagnostics and treatment of vertebrospinal pathologies were developed. Previous study showed that electrical stimulation of lumbar segments of the spinal cord in animals with complete spinal cord transection induced a well-coordinated weight-bearing locomotion. The present comparative study of motor activity triggered by electrical epidural stimulation of one or two segments of the spinal cord in spinal patients showed that stimulation of lumbar (L2-L4) or sacral (S2) segments facilitated generation of motor patterns of muscle activity. Combination of electrical stimulation with locomotor training resulted in the appearance of stepping patterns characteristic of normal walking and tonic activity of the muscles needed for body balance maintenance.     

Excitatory and inhibitory postsynaptic potentials in alpha-motoneurons produced during fictive locomotion by stimulation of the mesencephalic locomotor region

We tested the hypothesis that stimulation of the mesencephalic locomotor region (MLR) activates polysynaptic pathways that project to lumbar spinal motoneurons and are involved in the initiation of locomotion. Fictive locomotion was produced by MLR stimulation, and intracellular records of evoked postsynaptic potentials (PSPs) in alpha-motoneurons were computer analyzed. Stimulation of sites in the MLR that were maximally effective for the initiation of locomotion produced excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in all the motoneurons examined. The amplitudes of the PSPs increased as locomotion commenced. The EPSPs were largest during the depolarized phase of the step cycle, and in 17 of our 22 cells the EPSP was replaced by an IPSP of slightly longer latency during the hyperpolarized phase. The mean latency of the EPSPs measured from the stimulus artifact produced by stimulation of the MLR was 5.1 ms (3.0-7.0 ms). In all cases, the IPSP occurred 0.6 ms or more after the onset of the EPSP in the same cell. Later PSPs were sometimes observed as well. The effects of constant current injection on the membrane potential oscillations associated with fictive locomotion (locomotor drive potentials) were examined. The results showed that the amplitudes of the locomotor drive potentials (LDPs) could be affected by depolarizing and hyperpolarizing current injection. The data is consistent with the LDP having a predominant inhibitory component, which is more readily altered by current injection than is the excitatory component. The effect of constant current injections on the MLR-evoked PSPs was also examined, and it was observed that both EPSPs and IPSPs could be affected by the injected currents. The EPSPs increased in amplitude with constant hyperpolarizing current injection, and this fact rules out the possibility that the EPSP is actually a reversed IPSP. The IPSP was decreased in amplitude by hyperpolarizing current injection. Combined stimulation of the MLR and the ipsilateral high-threshold muscle or cutaneous afferents produced facilitation of both short- and long-latency MLR-evoked PSPs, suggesting that the two pathways share common interneurons. The possibility that the long-latency PSPs are produced by rapid oscillation in the locomotor central pattern generator is discussed. We concluded that MLR stimulation that evokes fictive locomotion produces both excitation and inhibition of spinal motoneurons. Spinal interneuronal systems are implicated and may be those involved in the initiation and control of locomotion. The probable relay sites for the descending pathway from the MLR to motoneurons are discussed.     

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.