Forelimb responses to cutaneous nerve stimulation during locomotion in intact cats

Brain Research, 329 (1985) 323-328

323

Elsevier BRE 20663

Forelimb responses to cutaneous nerve stimulation during locomotion in intact cats T. DREW and S. ROSSIGNOL Centre de Recherche en Sciences Neurologiques, Ddpartement de Physiologie, Facult~de Mddecine, Universitd de Montrdal, Montrdal, Qu& H3C 3T8 (Canada)

(Accepted October 23rd, 1984) Key words: locomotion - - cutaneous nerve stimulation - - forelimb muscles - - chronic cats - - electromyogram

The reflex responses of forelimb muscles to electrical stimulation of the cutaneous superficial radial nerve were recorded during treadmill locomotion in chronically implanted cats. In brachialis and cleidobrachialis (muscles which are active mainly during the swing phase) the responses were maximal during the swing phase and minimal or absent during the stance phase. In the long head of triceps which is active mainly during the stance phase, responses were also minimal during stance and maximal during swing. It is concluded that, for some muscles, the period of maximal reflex responsiveness can be out of phase with the period of the step cycle during which they are normally active. Mechanical or electrical stimulation of the skin of the dorsum of the hind foot of a spinal cat walking on a treadmill belt may evoke short latency (10-25 ms) ipsilateral responses in flexors which are maximal during swing and minimal or absent during stance. The same stimulation can also induce large responses in extensor muscles but only during the phase of the locomotor cycle during which they are active (stance) and not in the opposite phase (swing)11-13. Similar phase dependent responses to cutaneous stimulation have now been documented in several walking preparations not only for the ipsilateral stimulated hind1imb1,7-9,15,22,26,29 or forelimb2,21 but also for the hindlimb contralateral to the stimulation6,]4, 23-25. The same principle seems also to apply to the limbs of one girdle for inputs originating from the limbs of the other girdle21,27,28. As a general rule, the responses to cutaneous stimuli tend to reinforce the ongoing muscle activity so that they are largest when evoked during, or in close relation to, the period of locomotor activity of the muscles. There is thus an overall correspondence between the time when muscles are most likely to be activated by cutaneous inputs (reflex responsiveness) and their period of locomotor activation.

The present work suggests that the periods of reflex responsiveness and locomotor activity can be dissociated in some forelimb muscles of the intact cat ~valking on a treadmill. The superficial radial nerve (SR), which innervates skin overlying the dorsum of the forepaw, was stimulated through chronically implanted stainless steel electrodes held around the nerve by a polymer cuff] 6. The stimulus (a single pulse of 0.2 ms) was initially adjusted to threshold (T) defined as the minimum current necessary to cause the smallest perceptible flexion of the manually extended forelimb when the cat was sitting quietly. Stimuli at 1 x T evoked only very small electromyographic (EMG) responses ipsilaterally in the pure elbow flexor, brachialis (iBr) as seen in Fig. 1A. During the swing phase of locomotion, the same stimulus, however, elicited much larger excitatory responses (latency 8 - 1 0 ms) in this muscle (compare Fig. 1A and B). During stance, there was no detectable response in iBr (compare Fig. 1B and C). In the long head of triceps (iTri) which anatomically is an elbow extensor and a shoulder flexor there was no apparent response in either swing or stance. However, in cleidobrachialis (iC1B), an elbow and shoulder flexor, there was a clear inhibition (latency 16-23

Correspondence: S. Rossignol, Centre de Recherche en Sciences Neurologiques, D6partement de physiologie, Facult6 de M6decine, Universit6 de Montr6al, C.P. 6128, Succursale 'A', Montr6al, Qu6. H3C 3T8, Canada.

0006-8993/85/$03.30 © 1985 Elsevier Science Publishers B,V. (Biomedical Division)

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lS Fig. 1. Responses in forelimb muscles to stimulation of the SR nerve. In A-C, the stimulus was set at 1 x T and in D - F it was set at 2 × T. In each case the stimuli are shown twice at rest (A and D) and once in the swing (B and E) or stance (C and F) phase. During walking the stimulation was triggered, every 3 or 4 step cycles, by the activity in a selected muscle and was delayed appropriately to cover the whole of the walking cycle in steps of 100 ms (see also ref. 3). The electromyograms were recorded bipolarly with teflon-coated multistranded stainless steel wires chronically sewn into the belly of the muscles and led subcutaneously to multipin connectors cemented to the skull of the animal. The time base applies to all figures. ms) lasting from 30 to 60 ms which was followed by a p e r i o d of increased activity which slightly p r o l o n g e d the burst. O b s e r v a t i o n of simultaneously r e c o r d e d video tapes shows that the overall E M G response was translated mechanically into a brief increase in the flexion of the elbow. Stimuli at 2 × T given at rest (Fig. 1D) e v o k e d responses not only in iBr but also in iTri. Fig. 1E illustrates a typical response in these forelimb muscles when the SR stimulation arrived during the swing period of l o c o m o t i o n and thus during the p e r i o d of activity of iBr and iCIB, and, correspondingly during the p e r i o d of inactivity of iTri. The stimulation e v o k e d a response in iBr which was at the same latency as for stimulation at 1 × T but which was noticeably larger. The responses in iCIB followed the same p a t t e r n as

for stimulation at 1 × T, with the exception that the p e r i o d of increased activity after the inhibition was of larger amplitude. The effect of the stimulation on iTri, however, was completely different as there was now a clear excitation (latency 10-12 m s ) o f the muscle at a time when it is normally inactive in the locomotion cycle. O b s e r v a t i o n of the animal as well as video analyses have indicated that when the stimulation was given during swing, the progression of the stimulated forelimb was halted, the elbow and shoulder flexed and the digits and wrist ventroflexed. This initial response withdrew the foot backwards and upwards and was later followed by a s u p p l e m e n t a r y flexion which brought the limb forward again to place the foot on the belt. W h e n the same stimulus arrived during stance, there was no, or only a weak, response

325 in iTri (Fig. 1F) although this is the period of the locomotor cycle during which this muscle is active. Fig. 2A and B show the results of stimulation at 3.2 x T. In Fig. 2A, the pattern described in Fig. 1E is even clearer. There is now, however, also a small excitatory response (latency 8-10 ms) in iC1B which precedes the onset of inhibition. It should be noted that in other experiments this excitatory response in iC1B was much more prominent and could be evoked at a lower stimulus strength. Fig. 2B illustrates that stimulation during stance evoked only a weak excitation in iTri as well as a small out of phase response in iBr. Fig. 2C shows the amplitude of the responses recorded in the 3 muscles as a function of the phase of the step cycle in which the stimulation was given. The graph clearly demonstrates that in iBr and iCIB, the largest responses were evoked during the period of locomotion when they are active (see shaded rectangles). It should be noted that at this particular strength there was also a smaller response in iBr which persisted throughout the remainder of the cycle. More interestingly, however, the largest responses were also evoked in iTri at the time when the flexor muscles are active and thus during the period when the extensor muscles are silent. Thus for the amotoneurones of that muscle the period of maximal reflex responsiveness is out of phase with their period of activation during locomotion. Similar results were repeatedly found in 22 different sessions in two cats. In one of these cats and in 3 other cats, the forepaw was obstructed during swing using a metal rod to which was attached a microswitch which indicated the moment of contact. Both the E M G responses and the limb trajectory were similar to those described above suggesting that similar afferents are being activated by the electrical and the mechanical stimulation. Thus the present report gives an indication of the overall forelimb response strategy adopted by the intact walking cat when the forefoot hits an obstacle. When this occurs, the forefoot is initially elevated and withdrawn backwards before it is carried forwards and placed on the ground. This strategy resembles that seen in spinal cats when the hindlimb is obstructed during swing. The sequence of events in this latter preparation is such that the knee flexors are activated before the ankle and hip flexors12 thus result-

ing in an initial withdrawal of the foot backwards and upwards before the whole limb is brought forwards above the obstacle. This raising of the foot is mainly achieved using the knee flexors which are already active 29 and is thus in accord with the general correspondence between the period of locomotor activity and the period of reflex responsiveness seen in most hindlimb muscles. Contrary to this, to remove the forepaw from an obstacle the animal has to flex the shoulder by activating muscles such as the long head of triceps in a period of the step cycle during which it is inactive. The implication of this observation is that the period of reflex responsiveness of a muscle during locomotion can be largely dissociated from its period of locomotor activity. In the hindlimbs out of phase responses have also been described, particularly in ankle extensorsS.9,10, 29. One interpretation, provided by Wand et al. 29 is that the ankle extensors, activated together with ankle flexors, would lock the foot while the knee flexors pivot the foot upwards and backwards. In the forelimbs the data of Miller et al. 21 (their Fig. 6A) suggest that the triceps is also mainly activated out of phase. Again in the forelimbs, Matsukawa et al. 20 have shown that mechanical taps during swing usually evoke, in intact as well as in decerebrate cats, short latency responses in flexors and extensors. It appears then that during locomotion the reflex responsiveness of some muscles may be controlled independently of their recruitment in the locomotor cycle such that for some muscles, the periods of reflex responsiveness and locomotor activity would be in phase while in other muscles they could be out of phase. Similar observations were made during mastication in the rabbit where it was found that the jaw opening reflex brought about by the activation of the digastric muscle was maximal during the period of jaw closure, i.e. during the period of inactivity of the digastric muscle 17-19. It is thus concluded that the period of reflex responsiveness of muscles and their period of activity in a rhythmical movement may be two independently controlled processes. This is in agreement with the suggestion 2,22 that a-motoneurones of certain bifunctional muscles are driven by the central pattern generator as extensors during the stance phase but can also receive an indirect flexor command through flex-

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toral f e l l o w s h i p to T . D . T h e assistance of J. P r o v e n c h e r , G. B l a n c h e t t e , S. B e r g e r o n and R. B o u -

This w o r k was s u p p o r t e d by a g r o u p g r a n t f r o m t h e M e d i c a l R e s e a r c h C o u n c i l of C a n a d a and a p o s t - d o c -

1 Andersson, O., Forssberg, H., Grillner, S. and Lindquist, M., Phasic gain control of the transmission in cutaneous reflex pathways to motoneurones during 'fictive' locomotion, Brain Research, 149 (1978) 503-507. 2 Cabelguen, J.-M., Orsal, D., Perret, C. and Zattara, M., Central pattern generation of forelimb and hindlimb locomotor activities in the cat. In J. Szentagothai, M. Palkovits and J. Hamori (Eds.), Regulatory Functions of the CNS.

Motion and Organization Principles, Advances in Physiological Sciences, Vol. 1, Akademiai Kiado, Budapest, 1981, pp. 199-211. 3 Drew, T. and Rossignol, S., Phase dependent responses evoked in limb muscles by stimulation of the medullary reticular formation during locomotion in thalamic cats, J. Neurophysiol., 52 (1984) 653-675. 4 Duysens, J., Reflex control of locomotion as revealed by stimulation of cutaneous afferents in spontaneously walking premammillary cats, J. Neurophysiol., 40 (1977) 737-751. 5 Duysens, J. and Loeb, G. E., Modulation of ipsi- and contralateral reflex responses in unrestrained walking cats, J. Neurophysiol., 44 (1980) 1024-1037. 6 Duysens, J., Loeb, G. E. and Weston, B. J., Crossed flexor reflex responses and their reversal in freely walking cats, Brain Research, 197 (1980) 538-542. 7 Duysens, J. and Pearson, K. G., The role of cutaneous afferents from the distal hind-limb in the regulation of the step cycle of thalamic cats, Exp. Brain Res., 24 (1976) 245-255. 8 Duysens, J. and Stein, R. B., Reflexes induced by nerve stimulation in walking cats with implanted cuff electrodes, Exp. Brain Res., 32 (1978) 213-224. 9 Forssberg, H., Stumbling corrective reaction: a phase-dependent compensatory reaction during locomotion, J. Neurophysiol., 42 (1979) 936-953. 10 Forssberg, H., Phasic gating of cutaneous reflexes during locomotion. In A. Taylor and A. Prochazka (Eds.), Muscle Receptors and Movement, MacMillan, London, 1981, pp. 403-412. 11 Forssberg, H., Grillner, S. and Rossignol, S., Phase dependent reflex reversal during walking in chronic spinal cats, Brain Research, 85 (1975) 103-107. 12 Forssberg, H., Grillner, S. and Rossignol, S., Phasic gain control of reflexes from the dorsum of the paw during spinal locomotion, Brain Research, 132 (1977) 121-139.

c h o u x has b e e n i n v a l u a b l e . Discussions with D r . J.M. C a b e l g u e n h a v e b e e n m o s t helpful.

13 Forssberg, H., Grillner, S., Rossignol, S. and Wallen, P., Phasic control of reflexes during locomotion in vertebrates. In R. M. Herman, S. Grillner, P. S. G. Stein and D. G. Stuart (Eds.), Neural Control of Locomotion, Plenum Press, New York, 1976, pp. 647-674. 14 Gauthier, L. and Rossignol, S., Contralateral hindlimb responses to cutaneous stimulation during locomotion in high decerebrate cats, Brain Research, 207 (1981) 303-320. 15 Julien, C., Barbeau, H. and Rossignol, S., Gain changes in cutaneous reflexes during locomotion in the adult chronic spinal cat, Soc. Neurosci. Abstr., 8 (1982) 168. 16 Julien, C. and Rossignol, S., Electroneurographic recordings with polymer cuff electrodes in paralyzed cats, J. Neurosci. Meth., 5 (1982) 267-272. 17 Lund, J. P. and Olsson, K. A., The importance of reflexes and their control during jaw movement, Trends Neurosci., 6 (1983) 458-463. 18 Lund, J. P., Rossignol, S. and Murakami, T., Interactions between the jaw opening reflex and mastication, Canad. J. Physiol. Pharmacol., 59 (1981) 683-690. 19 Lund, J. P. and Rossignol, S., Modulation of the amplitude of the digastric jaw opening reflex during the masticatory cycle, Neuroscience, 6 (1981) 95-98. 20 Matsukawa, K., Kamei, H., Minoda, K. and Udo, M., Interlimb coordination in cat locomotion investigated with perturbation. I. Behavioral and electromyographic study on symmetric limbs of decerebrate and awake walking cats, Exp. Brain Res., 46 (1982) 425-437. 21 Miller, S., Ruit, J. B. and van der M6ch6, F. G. A., Reversal of sign of long spinal reflexes dependent on the phase of the step cycle in the high decerebrate cat, Brain Research, 128 (1977) 447-459. 22 Perret, C., Cabelguen, J.-M., Main characteristics of the hindlimb locomotor cycle in the decorticate cat with special reference to bifunctional muscles, Brain Research, 187 (1980) 333-352. 23 Rossignol, S. and Gauthier, L., Patterns of contralateral limb responses to nociceptive stimuli during locomotion, Soc. Neurosci. Abstr., 4 (1978) 304. 24 Rossignol, S., Julien, C. and Gauthier, L., Stimulus-response relationships during locomotion, Canad. J. Physiol. Pharmacol., 59 (1981) 667-674. 25 Rossignol, S., Julien, C., Gauthier, L. and Lurid, J. P., State dependent responses during locomotion. In A. Taylor and A. Prochazka (Eds.), Muscle Receptors and Move-

Fig. 2. In A and B the stimuli are given during swing and stance respectively, in the same cat as for Fig. 1 but on a different day. In C, the responses recorded in the 3 muscles (3.2 x T) are plotted as a function of the phase of the step cycle in which the stimulation was given. For this analysis, EMGs were digitized at 1 kHz and analyzed on a PDP 11/34 computer. The excitatory responses elicited in different periods of the step cycle were averaged and the EMG activity surpassing 90% of the average background level was integrated. The numerical values of these responses (n = 114) were expressed as a percentage of the maximal response amplitude observed in any one muscle and each point corresponds to the mean of 6-17 responses elicited during each period expressed in phases of the mean control step cycle. The shaded rectangles above indicate the mean duration (+ 1 S.D.) of the locomotor EMG burst of each muscle taken from 30 to 45 control cycles.

328 rnent, MacMillan, London, 1981, pp. 389-402. 26 Schomburg, E. D. and Behrends, H. B., Phasic control of the transmission in the excitatory and inhibitory reflex pathways from cutaneous afferents to a-motoneurones during fictive locomotion in cats, Neurosci. Left., 8 (1978) 277-282. 27 Schomburg, E. D., Behrends, H. B. and Steffens, H., Changes in segmental and propriospinal reflex pathways during spinal locomotion. In A. Taylor and A. Prochazka (Eds.), Muscle Receptors and Movements, MacMillan,

London, 1981, pp. 413-425. 28 Schomburg, E. D., Roesler, ,I. and Meinck, H. M., Phasedependent transmission in the excitatory propriospinal reflex pathway from forelimb afferents to lumbar motoneurones during fictive locomotion, NeuroscL Lett.. 4 (1977! 249-252. 29 Wand, P., Prochazka, A. and Sontag, K. H., Neuromuscular responses to gait perturbations in freely moving cats, Exp. Brain Res.. 38 (1980) 109-114.