Brain Research, 88 (1975) 367-371 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
How detailed is the central pattern generation for locomotion?
S. GRILLNER ANDP. ZANGGER* Department of Physiology, University of Gi~teborg, Gi~teborg (Sweden) (Accepted January 17th, 1975)
From investigations starting during the early part of last century and continuing until today, it has become clear that lower vertebrates 1,11,12 as well as mammals 1 including primates15, ~9 can use their limbs during walking after transection of all dorsal roots supplying the limb(s) investigated, i.e., without any segmental feedback and thereby through a central neuronal program. So far, no more objective comparisons have been performed to evaluate 'how normal' these movements are in terms of e.g. the time course of the different phases, the joint angles, the interlimb coordination or the detailed electromyographical pattern (for the newt cf., however, Sz6kely et aL~a). For mammals it is completely unknown if the central program contains the entire individualized activation pattern of the different muscles found in the intact animal or if it generates no more than an alternate activation of flexors and extensors. It has been suggestedS, 14 that the limb afferents (particularly from muscle spindles) could, via their action on the motoneurons, modify such a simple central program to result in the detailed pattern found in the intact animal. To test if the limb afferents are crucial in this role or if the central program is more detailed we have compared the E M G activity in walking cats before and after transection of all dorsal roots to one or both hindlimbs. The unmyelinated afferents recently described in the ventral roots 3 can hardly be thought to contribute any phasic information since the conduction time would be too long and they appear furthermore to originate in viscera 2 (bladder). The experiments (n = 13) have been performed on acute mesencephalic cats (precollicular and postmammillar transection), which can perform walking movements on a treadmill when a region around nucleus cuneiforme (P2, L4, 5.5-6.5 mm below the surface of the inferior colliculus) is stimulatedl°,~6,17. At low strength of stimulation the animal will walk; with increasing strength it can change to trot and finally gallop. The E M G pattern 7 and the kinematic parameters 13 appear identical to that of the walking intact catS, s. Monopolar stimulation with thin tungsten electrodes (tip 20-40 #m, R 20-100 kf~) was used (50 Hz, 7-140/aA, 0.5 msec square wave pulses). The head was fixed in a stereotaxic apparatus while the body was * Present address: Institut de Physiologic, Universit6 de Fribourg, P6rolles, 1700 Ftibourg, Switzerland.
368 s u s p e n d e d in r u b b e r straps w i t h the feet resting on the t r e a d m i l l belts. T h e E M G was r e c o r d e d b i p o l a r l y f r o m thin ( 1 0 0 / z m ) c o p p e r wires i n s e r t e d i n t o the muscles a n d i n s u l a t e d e x c e p t f o r the tips 1-2 m m (see ref. 6). T h e E M G s a n d o t h e r p a r a m e t e r s w e r e r e c o r d e d o n an 8 - c h a n n e l i n k w r i t e r ( s t r a i g h t f r e q u e n c y r e s p o n s e to 1200 H z ) . A l a m i n e c t o m y was p e r f o r m e d f r o m L3 to L7. D o r s a l r o o t t r a n s e c t i o n was m a d e intradurally under magnification.
Fig. 1. The effect of deafferentation on flexor muscles with different patterns of activity during locomotion. The EMG activity is shown from above in an ankle extensor (A. ext., lateral gastrocnemius), a hip flexor (H.fl., iliopsoas), a knee flexor (K.fl., semitendinosus) and another hip flexor, lateral sartorius, which in addition has a knee extensor effect. The left panel shows the activity with intact dorsal roots and the middle after ipsilateral transection of the dorsal roots (L3-$4) and the right the effect of transection of the same dorsal roots on the contralateral side. Below each panel is a normalized schematical representation of the activity in several (15) consecutive cycles. Each cycle starts with the onset of EMG activity in the extensor and the bars indicate the period of EMG activity. The bars for the different flexor muscles indicate in which part (~) oftbe stepcycle the muscles are active. The additional activity found during the extension phase (K.fl.) is indicated in the graph by two dots showing onset and termination of activity. After the deafferentation the termination of the muscle activity in the two H.fl. occurs somewhat later and the bars indicate the cessation of the main activity and the dots the complete cessation. This means that there is in fact an overlap between the flexor and extensor activity. In other experiments the termination of these muscles has been unchanged when comparing the pattern before and after deafferentation. The time calibration to the right applies to all records. The speed of the treadmill was 1.6 m/sec in the left panel and 2.0 m/sec under deafferented conditions.
369 Fig. 1 (left column) shows the EMG activity during locomotion in one ankle extensor and three flexors of the hindlimb. Below, the EMG activity of the different muscles in 15 consecutive step cycles is shown in a schematical and normalized way. One typical feature in the flexor group 5,7 is that the knee flexor semitendinosus (St) has only a short period of activity in the early 'flexor period' and a somewhat more variable period of activity during the extension phase. The slight variability in the pattern of activity during successive cycles is then apparent. The middle column shows the EMGs some minutes after transection of all dorsal roots (L3-$4) supplying this hindlimb. The short period of activity in the knee flexors remains as well as that during the extensor period. The pattern appears unchanged (see legend). It should be recalled that the other three legs walk on the treadmill. Finally (right column) after a bilateral transection the same main features remain although the pattern has become more variable. Hence it can be concluded that the characteristic short periods of activity in both the flexion and extension phase remain after transection of all afferents supplying the two limbs.
Fig. 2. The effect of ipsilateral deafferentation on muscles active during the extension phase. The electromyographical pattern of a knee (quadrieeps, Q) and ankle (lateral gastrocnemius, LG) extensor and extensor digitorum brevis (EDB) is shown before (left) and after (right) ipsilateral deafferentation (L3-$4). Below is shown a similar schematical representation as in Fig. 1 except that the cycle length is not normalized but the termination of each cycle is indicated by the dots in the upper series and shown in absolute time (abscissa). Note time calibration. The treadmill speed was 1.2 m/sec.
370 Fig. 2 shows a similar comparison of the activity in a knee (Q) and an ankle (LG) extensor and in extensor digitorum brevis (EDB) which has its main activity in the first part of the extension phase 4 and usually starts somewhat before the extensors although it is active throughout the stance phase. The same pattern is observed after dorsal root transection. From these findings it can be concluded that the striking differences in activation pattern between some muscles within one group as St versus other flexors (Fig. 1) or EDB versus other muscles active in the extension phase (Fig. 2) are programmed by a central pattern generator and not depend on the afferents originating from the limb(s) investigated. For this conclusion it is sufficient that the same pattern can at all be observed after deafferentation and indeed this is the general picture, Occasionally, however, the pattern can in a deafferented preparation be normal for one test period and then gradually or suddenly change to another stable pattern when e.g., the short flexor burst in St (cf. Fig. 1) disappears altogether, whereas the rather feeble and short activity observed in the extensor period becomes longer and very strong similar to an ordinary extensor as quadriceps. Somewhat later the pattern may revert to normal again. This study has considered mainly the timing of the muscles in relation to each other, and not tried to quantitate the relative amount of E M G activity in the different muscles. We have, on the other hand, in our records not observed any systematic changes after deafferentation. In summary the central program (unknown neuronal design) does not simply generate an alternate activation of flexors and extensors but a more delicate pattern that will sequentially start and terminate the activity in the appropriate muscles at the correct instance. The role of the afferents in this context is not primarily to control the timing of the muscle activity in the individual limb but may rather be to interact when external perturbations occur (see ref. 9). This work was supported by the Swedish Medical Research Council (Project No. 3026) and the Medical Faculty of G6teborg. Peter Zangger was supported from the Swiss National Foundation. The valuable assistance of Mrs. M. Svanberg is gratefully acknowledged.
1 BICKEL, A., Ueber den Einfluss der sensibelen Nerven und der Labyrinthe auf die Bewegungen
der Thiere, Pfliigers Arch. ges. Physiol., 67 (1897) 299-344. 2 CHVrON, G. L., VANCe, W. H., AVPL~BAUM,M. L., COGGESnALL,R. E., ANt) WILLIS,W. D., Responses of unmyelinated afferents in the mammalian ventral root, Brain Research, 82 (1974) 163-167. 3 COGG~SnALL,R. E., COULTER,I. D., ANDWILLm,W. D., Unmyelinated fibers in the ventral root, Brain Research, 57 (1973) 229-233. 4 ENOBERG,I., Reflexes to foot muscles in the cat, Actaphysiol. scand., 62, Suppl. 235 (1964). 5 ENGBERG, I., AND LUNDBERG, A., An electromyographic analysis of muscular activity in the hindlimb of the cat during unrestrained locomotion, Acta physioL scand., 75 (I969) 614-630. 6 FORSSBERG,H., ANDGRtLLNER,S., The locomotion of the acute spinal cat injected with Clonidine i.v., Brain Research, 50 (1973) 184-186. 7 GAMBARIAN,P. P., ORLOVSKY,G. N., PROTOPOPOVA,T. Y., SEVERIN,F. V., AND SHIK, M. L., The activity of muscles during different gaits and adaptive changes of moving organs in family
371 Felidae. Morphology and ecology of vertebrates, Proc. Inst. Zool. Acad. Sci. U.S.S.R., 48 (1971) 220-239. 8 GOSLOW,G. E., JR., REINraN6, R. M., ANDSTUNT, D., The cat step cycle: Hind limb joint angles and muscle lengths during unrestrained locomotion, J. Morph., 141 (1973) 1-41. 9 GRILLNER,S., Locomotion in vertebrates - - central mechanisms and reflex interaction, Physiol. Rev., (1975) in press. 10 GRILLNER,S., AND SI-IIK,M. L., On the descending control of the lumbosacral spinal cord from the 'mesencephalic locomotor region', Acta physiol, scand., 87 (1973) 320-333. 11 HARCOMnESMITH,E., AND WYMAN,R. J., Diagonal locomotion in de-afferentated toads, J. exp. Biol., 53 (1970) 255-263. 12 HOtST, E. yoN, Erregungsbildung und Erregungsleitung im Fischrfickenmark, Pfliigers Arch. ges. Physiol., 235 (1935) 345-359. 13 KUI~A6IN,A. S., ANDSHIK,M. L., Interaction of symmetrical limbs during controlled locomotion, Biofizika, 15 (1970) 171-178 (Engl. transl.). 14 LffNDB~RG,A., Reflex Control of Stepping. The Nansen Memorial Lecture V, Universitetsforlaget, Oslo, 1969, pp. 1-42. 15 MUNK, H., Ober die Folgen des Sensibilit~itsverlustes der Extremit~it fiir deren Motilit~it, S.-B. Akad. K. Preuss. Wiss., (1903) 1038-1077. 16 Sm~:, M. L., ORLOVSKY,G. N., AND SEWRIN, F. V., Organization of locomotor synergism, Biofizika, 11 (1966) 1011-1019 (Engl. transl.). 17 SHIK, M. L., SEWRIN, F. V., AND ORLOVSKV,G. N., Control of walking and running by means of electrical stimulation of the mid-brain, Biofizika, 11 (1966) 756-765 (Engl. transl.). 18 SZ~KELY,G., CZAR, G., AND VOR6S, G., The activity pattern of limb muscles in freely moving normal and deafferented newts, Exp. Brain Res., 9 (1969) 53-62. 19 TAUB, E., AND BERMAN,A. J., Movement and learning in the absence of sensory feedback. In S. J. FREEDMAN(Ed.), The Neurophysiology o f Spatially Oriented Behavior, Dorsey Press, Homewood, Ill., 1968, pp. 173-192.