(Received 1 August 1988)

Transcription

1 Journal of Physiology (1989), 410, pp With 3 text-figures Printed in Great Britain THE ORGANIZATION OF HETEROGENIC REFLEXES AMONG MUSCLES CROSSING THE ANKLE JOINT IN THE DECEREBRATE CAT BY T. RICHARD NICHOLS From the Department of Physiology, Emory University, Atlanta, GA 30322, USA (Received 1 August 1988) SUMMARY 1. Mechanical actions of heterogenic (intermuscular) reflexes arising from proprioceptors in flexor and extensor ankle muscles were measured in intercollicular and premammillary decerebrate cats. Length inputs were applied to the freed tendons of one of a pair of muscles crossing the ankle joint and resulting changes in force in both muscles were measured. Interactions between autogenic and heterogenic reflexes were studied by applying length changes to both muscles. 2. A consistent asymmetry was observed in the heterogenic inhibition between the single-joint antagonists soleus and tibialis anterior (TA). Inhibition from soleus to TA was weak or absent during the reflex activation of TA. In contrast, a strong heterogenic inhibition was consistently observed from TA to soleus during the activation of soleus by a crossed-extension reflex. The effect of this inhibition in the intact joint is to increase the apparent mechanical stiffness of soleus. 3. Mutual synergism among soleus, medial gastrocnemius (MG) and lateral gastrocnemius (LG) was demonstrated only at low to moderate forces by the observation of excitatory reflexes among them. During a naturally or electrically evoked crossed-extension reflex, however, a unidirectional inhibitory reflex from MG and LG to soleus was observed. This inhibition increased with force in MG or LG. These results suggest that the knee and ankle joints become more tightly linked mechanically at high forces since the stiffness of the biarticular gastrocnemius muscle predominates over that of the uniarticular soleus. 4. Under quiescent conditions (no resting muscle activation), mutual synergism was obeyed among the ankle extensors soleus, LG and MG and also between the pretibial flexors TA and extensor digitorum longus (EDL). Moreover, inhibition was generally observed between a pretibial flexor and an ankle extensor. Departures from this expected pattern of heterogenic reflexes occurred when the muscle groups were activated by crossed-extension and flexion reflexes. Reflexes onto soleus, TA and EDL reversed in sign or increased in magnitude. 5. The observed patterns of reflex connectivity among the ankle flexors and extensors were similar in both intercollicular and premammillary preparations, although changes in reflex strength were sometimes noted in cases where a second, lower transection was performed during the experiment. 6. It is argued from the large magnitudes of certain heterogenic reflexes that the mechanical response properties of muscles crossing the ankle joint in the intact animal are not dominated by autogenic reflexes and intrinsic mechanical properties.

2 464 T R. NICHOLS Rather, proprioceptive feed-back from heteronymous muscles appears to make a major contribution to the mechanical responses of a given muscle. Further, heterogenic reflexes in general are state dependent and must be treated explicitly in any model of spinal reflex action. INTRODUCTION The analysis of the mechanical actions of proprioceptive, spinal reflexes has largely been confined to autogenic reflexes, which influence the same muscle from which they arise (Houk & Rymer, 1981; Rack, 1981). Although there is considerable controversy over the functional interpretation of the observed mechanical actions of autogenic reflexes (Stein, 1982; Berkinblit, Feldman & Fukson, 1986) it has been proposed that these pathways participate in determining the stiffness of muscles and therefore of an entire limb (Nichols & Houk, 1976; Hoffer & Andreassen, 1981). The extensive electrophysiological work of Eccles, Lundberg, Jankowska and others (Baldissera, Hultborn & Illert. 1981) has revealed, however, that muscles acting about the same and distant joints are extensively interconnected by proprioceptive reflex pathways, which will be referred to here as heterogenic. Presumably, heterogenic reflexes serve to co-ordinate muscular action as suggested by the classically defined patterns of mutual excitation between synergists and inhibition between antagonists (Creed, Denny-Brown, Eccles, Liddell & Sherrington, 1932; Lloyd, 1946; Eccles, Eccles & Lundberg. 1957). There is, in addition, evidence from human studies that manipulating heterogenic inputs can interfere with the normal execution of movements (Capaday & Cooke, 1983) and that heterogenic reflexes interact powerfully with autogenic reflexes (Matthews & Watson, 1981). It is unlikely, therefore, that the net mechanical response properties of the intact limb are determined solely by the summed actions of autogenic reflexes and the intrinsic mechanical properties of muscle. In contrast to the extensive functional studies of autogenic reflex action referred to above, there has been little work done on the mechanical actions of heterogenic reflexes and on the contributions these pathways might have on the resultant mechanical properties of joints and limbs. It is possible in some cases to predict the actions of reflex pathways based on the known circuitry. For example, reciprocal Ia inhibition (Baldissera et al. 1981) should, in principle, enhance the stiffness of a joint (Houk & Henneman, 1974) by increasing the stiffness (change in force per unit change in length) of the muscle receiving the inhibition. Few studies, however, have been done to document these effects and the manner in which heterogenic and autogenic reflexes interact. Using an extension of the technique employed by Nichols & Houk (1976) to partition the mechanical properties of muscle into the intrinsic mechanical properties of contracting motor units and an autogenic reflex component, Nichols (1987 a) has shown that the mechanical actions of heterogenic reflexes can be measured if two muscle pullers are employed. The further application of this technique to a number of different heterogenic reflexes is the subject of the present report. A qualitative map of functional reflex connectivity among the major flexors and extensors of the cat's ankle joint is given. The relationship of this map to the known spinal circuitry

3 HETEROGENIC REFLEXES IN DECEREBRA TE CA TS and its functional implications are briefly discussed. Some of the results have been published in preliminary form (Nichols, 1985, 1986). 465 METHODS The methods have been given in detail elsewhere (Nichols, 1987 a), so only a brief description is provided here. The results were drawn from experiments on thirty-five cats of either sex weighing 3-55 kg. Decerebration at the premammillary or intercollicular levels was performed under halothane anaesthesia and all brain tissue anterior to the transection was removed from the cranium. Up to four muscles crossing the right ankle were exposed and carefully separated in a given preparation. These included gastrocnemius or the medial (MG) or lateral heads (LG) of gastrocnemius, plantaris, soleus, tibialis anterior (TA) and extensor digitorum longus (EDL). Placement of muscles at the proper relative lengths was accomplished using thread markers around the fibula and the individual tendons. The foot was disarticulated and cuff electrodes were placed around the ipsilateral sural nerve and around the ipsilateral and contralateral posterior tibial nerves near the ankles. The remaining innervation of the leg was left intact. Temperatures of the core and of the right leg were maintained at C by heating pads and a lamp. The right leg was held firmly by a clamp on longitudinal pins in the tibia and femur and by a clamp around the lateral and medial malleoli. The muscles were kept moist with gauze sponges soaked in liquid paraffin. Electromyographic (EMG) electrodes consisting of insulated 100,um silver wires bared at the tips were placed in the dissected muscles about 0 5 cm apart. Signals from the EMG preamplifiers were rectified and then filtered with a low-frequency cut-off of 6-4 Hz. The tendons from one muscle pair were connected through semiconductor strain-gauge myographs to the pulleys of two servocontrolled printed motors using braided steel cables. Length inputs were commanded by two programmable ramp generators. Mechanical and EMG data were collected directly on a multichannel chart recorder and on a PDP-1 1/73 computer at a sampling rate of 500 s-'. Data were obtained by eliciting a series of mechanical responses in a quiescent (no resting EMG) or activated preparation. Ramp length inputs consisted of a constant velocity phase of 100 ms duration to an amplitude of 4 mm followed by a plateau phase of 300 ms and a return to the starting length. The muscle system was activated in one of two ways using electrical stimulation. First, the extensor group was activated and flexor group inhibited (crossed-extension pattern) by stimulating the contralateral tibial nerve at 50 Hz at a strength of 2-5 times threshold for the minimal reflex effect. It was found in these experiments that varying the stimulus strength resulted in gradations in the strength of the contraction without otherwise affecting the size of autogenic reflexes or pattern of reflex interactions. Secondly, the flexor group was activated by stimulating the distal, ipsilateral tibial nerve. Crossed-extension reflexes were also evoked by manipulating and squeezing the contralateral leg. Reflex effects were studied using various combinations of length inputs as illustrated in Figs 1 and 2. For the systematic evaluation of reflex effects shown in Tables 1 and 2 and in Fig. 3, the relative strengths in the activated state of the heterogenic inputs were estimated in the following standard way. Under quiescent conditions or during a given crossed-extension or flexion reflex, the muscle receiving the heterogenic input (designated the recipient) was stretched to obtain the response due to autogenic reflex and intrinsic components (Nichols & Houk, 1976). On alternate stretches of the recipient, the recipient and the muscle from which the heterogenic input was obtained (designated the donor) were stretched together regardless of the in situ mechanical coupling between the muscles. For cases in which the sign of the heterogenic input did not change as a function of force during the contraction of the recipient, the extent to which stretching the donor enhanced or reduced the response of the recipient was then evaluated at the end of the 300 ms plateau phase of the ramp by comparing the magnitudes of the ensemble averages (Nichols, 1987 a). For cases in which the sign of the heterogenic input changed with force during the contraction, individual responses were compared at the highest forces obtained. For all cases, initial lengths were chosen to maximize the heterogenic effects.

4 466 T. R. NICHOLS A FS AFS C LT B AFS LS ''l F,. - LT Fig. 1. Heterogenic inhibition from TA to soleus. A, soleus was held isometrically at a length corresponding to a joint angle of approximatelv 110 deg and was activated by stimulating the contralateral tibial nerve distally at 50 Hz. Stimulation began at the time denoted by the arrow and continued throughout the illustrated sequence. TA was subjected to ramp-and-hold stretches starting from a length corresponding to 110 deg. Ramps were 4 mm in amplitude with a duration of 100 ms and a hold phase of 300 ms. Traces are, from the top: F,. force of soleus; AFs, amplified force, reset to baseline prior to each perturbation; E,. EMG recording from soleus, rectified and low-pass filtered at 6 4 Hz; LT. length of TA. B, in each trial, soleus was stretched 4 mm, and, on alternate trials, TA was also released 4 mm mimicking in situ mechanical coupling. As in A, stimulation of the contralateral tibial nerve continued throughout the run. Initial length corresponded to an ankle angle of about 110 deg. Calibration bars: 10 N vertical (top trace only). 1 s horizontal. RESULTS The heterogenic reflex effects reported here could be divided into two classes depending upon whether or not the sign of the reflex varied with the force of either the recipient or donor muscle. Figure 1 illustrates the inhibition from TA to soleus which is an example of a force-independent heterogenic reflex. In the example shown in Fig. 1 A, soleus and TA were held at lengths which correspond approximately to an ankle angle of 110 deg (Goslow, Reinking & Stuart, 1973). The soleus muscle was

5 HETEROGENIC REFLEXES IN DECEREBRA TE CATS selectively activated using a crossed-extension reflex and 4 mm stretches were delivered to the inhibited TA (force record not shown) every 4-5 s. The heterogenic inhibition from TA to soleus is evident in the two force traces and in the EMG record. The magnitude of heterogenic inhibition from TA to soleus varied over a wide range from preparation to preparation, and tended to increase in premammillary animals subjected to a subsequent intercollicular transection during the experiment. In the converse experiment, in which TA was activated with a flexion reflex, the stretch of soleus produced little or no heterogenic inhibition in TA. The interaction of autogenic and heterogenic reflexes in the more physiological context of reciprocal movements between TA and soleus is illustrated in Fig. 1B. Soleus was activated using the crossed-extension reflex and the starting lengths of both muscles corresponded to a slightly plantar-flexed ankle angle of 110 deg. A protocol was used in which stretches of soleus alone were alternated with stretch of soleus and simultaneous release of TA. Length changes of equal magnitude were used since the moment arms of the two muscles are similar in the middle range of joint movement (Goslow et al. 1973; Nichols, 1985). Note that the reciprocal mechanical coupling leads to an enhancement of the stretch response and, therefore, the stiffness of soleus due to reduced heterogenic inhibition from TA upon its release. In this case, the enhancement amounted to about 20 %. A striking feature of the heterogenic inhibition between soleus and TA was its asymmetry. Under quiescent conditions, where there was little or no background activity in either muscle, heterogenic inhibition between soleus and TA could be demonstrated in some experiments to be bidirectional (Table 1 and Fig. 3, left panel). In the presence of a reciprocal pattern of activation, however, heterogenic inhibition appears to be essentially unidirectional from TA to soleus (see Table 2 and Fig. 3, right panel). In contrast to the heterogenic reflex from TA to soleus, which was inhibitory over all conditions explored in these experiments, certain heterogenic reflexes changed sign as a function of muscle force. An example is shown in Fig. 2. The initial lengths of soleus and gastrocnemius were made to correspond to a knee angle of about 110 deg and an ankle angle of 90 deg. Both muscles were activated using a crossedextension reflex and 4 mm stretches of soleus alone were alternated with 4 mm stretches of gastrocnemius and soleus. The latter condition is approximated during lengthening contractions of gastrocnemius and soleus during the trotting step cycle (Goslow et al. 1973), although the stretch of gastrocnemius is slightly less due to flexion at the knee. At low forces, which are portrayed on the right in Fig. 2, stretching gastrocnemius enhanced the response of soleus to stretch both at the termination of the ramp phase of stretch ('dynamic' component) and at the end of the plateau phase ('static' component). From experimental runs in which gastrocnemius (or MG or LG) served as the recipient and soleus the donor, it was shown that stretching soleus also enhanced the stretch response of gastrocnemius. That is, the two muscles function as mutual synergists at low forces. The earlier events during the contraction portrayed in Fig. 2 show, however, that an inhibitory reflex component from gastrocnemius to soleus is present and decreases as force decreases. The dynamic response is less affected than the static component, 467

6 468 T R. NICHOLS which may be a reflection of the action of the monosynaptic reflex in soleus which, due to its rapidity of transmission, is initially unopposed by polysynaptic inhibitory reflex action. The excitatory reflex from soleus to gastrocnemius was maintained even at high forces as illustrated by the excitatory responses which can be seen in the AFS I Es s FG EG 6W LG r\ Fig. 2. Force-dependent heterogenic reflex from gastrocnemius to soleus. Soleus and gastrocnemius were activated by stimulating the contralateral tibial nerve distally at 50 Hz and 5x threshold. Stimulation started just prior to illustrated part of run and continued throughout the run. Soleus was stretched in each trial and also gastrocnemius on alternate trials. Initial lengths corresponded to a 90 deg ankle angle and a 110 deg knee angle. Ramp parameters were as in Fig. 1. Traces, from the top, are: F., soleus force; AF8, amplified and reset soleus force; Es, EMG of soleus; Ls, length of soleus; FG, force of gastrocnemius; EG, EMG of gastrocnemius; LG, length of gastrocnemius. Calibration bars: 10 N vertical (top trace only), 1 s horizontal. Forces in both muscles decayed to resting tension by the end of the illustrated run. Note that the dynamic force response and especially the static response of soleus were inhibited at high forces and enhanced at low forces by stretching gastrocnemius. Note also the excitatory responses in gastrocnemius to stretching soleus alone. force trace of gastrocnemius (Fig. 2) when soleus was stretched alone. A similar pattern of results was observed using either head of gastrocnemius individually, although the inhibition was greater from MG to soleus than from LG to soleus (see Table 1). This pattern of heterogenic interaction between soleus and gastrocnemius (or LG or MG) was observed in thirteen premammillary and intercollicular preparations. The force at which net inhibition succumbed to net excitation varied considerably

7 HETEROGENIC REFLEXES IN DECEREBRATE CATS from preparation to preparation, and in a few cases inhibition of the static component of the response occurred at low forces with no crossed-extension reflex. In these cases, the inhibition could be reduced partially or completely by decreasing the initial length of gastrocnemius, LG or MG. In three experiments where a second TABLE 1. Magnitudes of heterogenic inputs in quiescent state Recipient Donor LG MG P Sol TA EDL LG , () (1) (4) (1) (1) MG +49,+50-10, ,+15 0, (2) (5) (4) (6) (3) P 0 0, ,-50 0, (1) (4) (2) (2) (2) Sol +15,+50 0,+15 O,+5 0, (4) (7) (3) (1)(1) TA -5,-20 0, , , (3) (6) (1) (20) (2) EDL 0,-40 0,-20 0,-20-5, (2) (4) (3) (2) (1) Quiescent 469 Data on which the graphs in the left panel (quiescent state) of Fig. 3 are based. The average percentage by which the response of the recipient muscle to 4 mm stretch is increased (+) or decreased (-) by the simultaneous 4 mm stretch of the corresponding donor muscle is indicated in each cell. The top row of numbers in each cell show the range of values, the middle row shows the average and standard deviation, and the bottom row indicates the number of preparations frwhich the data were pooled. transection was used to convert a premammillary to an intercollicular preparation, the pattern was unchanged but the force at which net inhibition succumbed to net excitation was lower following the transection. It was concluded from these experiments that, at high extensor forces, the in situ stiffness of soleus is reduced by an inhibitory component from gastrocnemius, while the heterogenic reflex from soleus to gastrocnemius enhances the in situ stiffness of gastrocnemius over all conditions. Figure 3 summarizes, in bar graph form, the signs and average magnitudes of autogenic and heterogenic reflexes for several major flexors and extensors crossing the ankle joint. These reflexes were measured under quiescent conditions, in which little or no background activity was present, and under conditions of powerful activation during crossed-extension and flexion reflexes. Each cell of the matrix represents a reflex from the muscle labelling the corresponding row to the muscle

8 47i0 T. R. XICHOLS labelling the corresponding column. The heights of the bars are proportional to the percentage by which the heterogenic input increases or decreases the total autogenic and passive responses of the muscle. Tables 1 and 2 provide the quantitative basis (see Methods) for the left and right panels, respectively, of Fig. 3. TABLE 2. MIagnitudes of heterogenic inputs in activated states Recipient Donor LG M(IG P Sot TA EDL LG +5,+5 0,-6 0, (2) (2) (3) (1) (1) MCG +30,+50-8?-20-10, ,+50 0, (2) (4) (6) (4) (4) I , (1) ~~(2) (3) (1) (1) Sol +25, ,+5 0, (3) (4) (3) (14) (2) TA -5-10,-20 0,-5-6,-50 0, (1) (3) (2) (19) (2) EDL ,-25-5,-30-10, (1) (1) (3) (6) (2) Extension Flexion Data on which the graphs in the right panel of Fig. 3 (activated state) are based. In these cases, the preparations were activated either by crossed-extension or flexion reflexes. For cases in which the signs of the reflexes changed upon activation, the values given are those obtained at the highest forces in the indicated number of preparations. In both quiescent and activated conditions, all six muscles showed excitatory autogenic reflexes. Net autogenic inhibition was never observed in these preparations. WVith regard to the excitatory interactions under quiescent conditions, there was good agreement between the results of Eccles et al. (1957) in which monosynaptic linkages were established, and the data presented here. In both studies, for example, strong excitation was found from plantaris to soleus, but it was weak from soleus to plantaris. The monosynaptic, excitatory interactions between MG and plantaris were very weak in the study of Eccles et al. (1957), whereas the net heterogenic effects were found to be inhibitory in the experiments reported here. With regard to the heterogenic interactions between the uniarticular soleus and TA, heterogenic inhibition from TA to soleus was observed in every case under quiescent conditions, but the inhibition from soleus to TA was observed in only five of eleven cases. During the crossed-extension reflex, heterogenic inhibition from TA to soleus remained strong but during the flexion reflex the inhibition from soleus to TA was always immeasurable or very weak.

9 HETEROGENIC REFLEXES IN DECEREBRA TE CA TS The organization of heterogenic reflexes from multijoint muscles onto soleus and TA was more complex. During the crossed-extension reflex, the inputs from MG, LG and plantaris onto soleus showed a transition from excitation to inhibition at higher forces, while the inputs from soleus onto MG, LG and plantaris remained unchanged. 471 Quiescent Activated LG MG p Sol TA EDL LG MG P Sol TA EDL LG MG P Sol TA EDL U U- --I- _-1 r-- -I _Elr--iF1 L r--- r JZZLU LG MG p Sol TA EDL r.-l I I m m r-.=. - l - U - =~~~~~~~M l- 1 JIZZL7 m-- E L -i IZZI a Extension ' Li Flexion -J Fig. 3. Patterns of autogenic and heterogenic actions in quiescent and activated states. Each cell represents a reflex interaction from the muscle indicated to the left of the corresponding row (donor) to the muscle indicated at the need of the corresponding column (recipient). The height of the bar in each cell indicates the average percentage increase (filled bar) or decrease (open bar) of the stretch response of the recipient brought about by the simultaneous stretch of the donor muscle, with 100 % change equivalent to the full height of the cell. The double lines separate muscles in the anterior and posterior anatomical compartments. In the quiescent state, there was little or no resting activity and no attempt was made to activate the muscles. The right matrix represents two different activated conditions, crossed-extension reflex and flexion reflex. Results from both premammillary and intercollicular decerebrate cats were pooled. LG, lateral gastrocnemius; MG, medial gastrocnemius; P, plantaris: Sol, soleus; TA, tibialis anterior; EDL, extensor digitorum longus. During the flexion reflex, on the other hand, heterogenic inhibition from LG, MG and plantaris to TA (and EDL in the case of MG) underwent a transition to heterogenic excitation. The interactions among LG, MG and plantaris were not affected by the conditions of activation in these experiments. The muscles LG and MG were organized as mutual synergists while the interactions with plantaris were weak or inhibitory. The heterogenic reflexes involving the multiarticular EDL were somewhat more complex than those involving TA. As in the case of TA, strong heterogenic inhibition from EDL to soleus was observed both in the quiescent preparation and during the crossed-extension reflex. On the other hand, the mechanical responses of EDL were virtually independent of mechanical changes in soleus under these two conditions. It was sometimes possible, however, to co-activate soleus and EDL using a weak

10 472 T R. NICHOLS crossed-extension reflex. During the co-contraction of these two muscles, the pattern of heterogenic inhibition from EDL to soleus and heterogenic excitation from soleus to EDL was observed. Co-activation of soleus and TA has been achieved in onlv two instances by peripheral nerve stimulation, and in those cases heterogenic excitation from soleus to TA was not observed. The heterogenic reflexes between TA and EDL were also complex. Mutual excitation was observed under quiescent conditions. while mutual inhibition appeared during the flexion reflex. Given the close mechanical association of TA and EDL, however, it is possible that movement of one muscle could produce an artifactual response in the other by direct mechanical interaction. This possibility was checked by repeating the study during electrical stimulation of TA and EDL after transecting the common peroneal nerve. There was indeed a small mechanical effect but it was insufficient in magnitude to account for the inhibition observed when the reflexes were intact. To further support the reflex basis of the inhibition, ramp stretches of high velocity (100 mm/s) were used. Because of the transmission delay of the reflex and the lagging properties of the muscle, the intrinsic mechanical response of the muscle was exposed for approximately the first 20 ms of the response (Nichols & Houk. 1976). The reflex component, but not this intrinsic response, was altered by the stretch of the other muscle. Similar control experiments were performed during the study of other reflex interactions to ensure that the observed interactions were not due to mechanical artifact. For example, soleus and TA were thrown into simultaneous activity during a strychnine seizure. In this condition, no signs of reflex activity were noted in the EMG or in the mechanical records, and the inhibition from TA to soleus was absent. DISCUSSION An important result from these experiments is the finding that the sign of the net action of some heterogenic reflexes depends upon the force exerted by one of the muscles involved. The signs of autogenic reflexes, heterogenic reflexes onto gastrocnemius and plantaris and the heterogenic reflexes from the ankle flexors onto soleus were independent of activation level. On the other hand, the heterogenic reflexes from gastrocnemius and plantaris onto soleus, TA and EDL changed sign depending on the state of activation. Several observations indicate that these transitions in net reflex sign depend on the initial conditions of activation and not on the source of the input used to activate the muscle system. First, the reported pattern of reflexes during extensor activation was observed during both electrically evoked and naturally evoked crossed-extension reflexes. Second, the inhibition from gastrocnemius to soleus exhibited the same pattern of force dependence whether evoked by stimulation of either the mixed tibial or the cutaneous sural nerve. Third, this inhibition was observed in some preparations to occur at low forces even without electrical stimulation of peripheral nerves, so it was not dependent upon the electrical stimulation of a particular group of afferents. These observations support the working hypothesis that the organization of heterogenic, proprioceptive reflexes depends mainly on the initial conditions in the relevant musculature rather than on the source of the input. Inputs can, therefore,

11 HETEROGENIC REFLEXES IN DECEREBRA TE CATS affect the organization of heterogenic reflexes indirectly by affecting the pattern of muscle activation. The observed pattern of reflexes was similar in different preparations and in animals with different levels of transection. The similarity in reflex pattern was in evidence despite the different behavioural repertoires of the premammillary and intercollicular decerebrate cat (Duysens, 1977). The effect of lowering the level of transection was not to change the patterns of reflex interaction shown in Fig. 3. but rather to change the gain of autogenic reflexes (cf. Nichols & Steeves, 1986) and to change the force at which the transition from net inhibition to net excitation occurred (see Results). Although the reported patterns were present in both intercollicular and premammillary preparations, it is possible that the organization revealed in these experiments is peculiar to the decerebrate state and not intrinsic to the spinal cord. That is, the observed pattern of reflexes could be determined by the levels of activity in various descending pathways in the decerebrate preparation. In recent experiments, however, patterns similar to those described here for soleus, TA and gastrocnemius were found in both legs of cats with chronic hemisections of the lumbar spinal cord (Munson, Ritz, Sypert & Nichols, 1988). Further, in cats with complete transections at low thoracic levels (Cope & Nichols. 1988), inhibitory reflexes among soleus, TA and gastrocnemius were suppressed or absent, but no reflexes different in sign from those reported above were observed. It appears, therefore, that the patterns of heterogenic reflexes described in this paper are intrinsic to the spinal cord. Reflex mechanisms The speed (40 mm/s) and duration (100 ms) of the ramp length changes used in these experiments correspond to the lengthening contractions of the ankle extensors observed during walking in the intact cat (Goslow et al. 1973), and they are slow enough to evoke responses of the tonic stretch reflex (Liddell & Sherrington, 1924; Nichols & Houk, 1976; Nichols, 1985). A number of reflex pathways can therefore be expected to have contributed to the observed responses (Binder, Houk, Nichols, Rymer & Stuart, 1982). With the exception of the inhibitory interactions between the triceps surae group and plantaris, the pattern of reflex interactions observed in the quiescent preparations can provisionally be attributed to pathways originating from muscle spindle receptors (Lloyd, 1946; Eccles et al. 1957). This conclusion is strengthened by the finding that the heterogenic inhibition from TA to soleus is larger when TA is stretched than when released (Nichols, 1987 a), which matches the asymmetry in response properties of primary endings (Houk, Crago & Rymer, 1981). The pattern of mutual heterogenic inhibition between TA and soleus under quiescent conditions suggests the spinal mechanism of postsynaptic reciprocal inhibition arising from Ia afferents (Fu, Hultborn, Larsson & Lundberg, 1978; Baldissera et al. 1981). Contributions of presynaptic inhibition of the I a inputs onto soleus motoneurones from the afferents of TA and EDL (Eccles, Eccles & Magni, 1961; Eccles, 1964) are also suggested, however, because (1) heterogenic inhibition from TA and EDL to soleus does not become weaker during extensor activation when the flexor-coupled Ia inhibitory interneurones should be inhibited (Hultborn, 473

12 474 T. R. NICHOLS Illert & Santini, 1976) and (2) presynaptic inhibition is stronger from flexor afferents to extensor motoneurones than the other way round (Eccles, 1964). The relative contributions of pre- and postsynaptic inhibition to heterogenic inhibition in this context, however, remain to be clarified. The force-dependent, heterogenic inhibition from gastrocnemius to soleus suggests the action of a force-dependent inhibitory pathway working in parallel with the heterogenic excitation from gastrocnemius to soleus. It has been shown previously that, when gastrocnemius is made to undergo decaying contraction by stimulating the sural nerve, the transition from net inhibition to net excitation still occurs in the heterogenic reflex to soleus even though the force in soleus remains relatively constant (Nichols, 1987 b). Therefore, the heterogenic inhibition appears to depend mainly on the force in gastrocnemius rather than the force in soleus. A possible mechanism is that Golgi tendon organs in gastrocnemius are recruited into activity as motor unit recruitment progresses (Houk & Henneman, 1967; Crago, Houk & Rymer, 1982). Another possibility is that recurrent inhibition from the large motor units in gastrocnemius may act preferentially on the smaller motor units in soleus (cf. Granit, Pascoe & Steg, 1957; Eccles, Eccles, Iggo & Ito, 1961). The relatively small effect of the heterogenic reflex on the dynamic response is likely to be due to the initially unopposed actions of the monosynaptic reflex and the long relaxation time of the soleus muscle (Grillner, 1972). Implications for limb biomechanics Several of the heterogenic reflexes described here are of sufficient magnitudes as to suggest that the stiffnesses of muscles in the intact limb are not dominated by the stretch reflex but are strongly dependent on heterogenic inputs from muscles which act at the same and distant joints. Since interjoint co-ordination is determined in part by the distribution of stiffnesses about the joints, heterogenic reflexes would seem to constitute an important mechanism for controlling interjoint co-ordination. This role of heterogenic reflexes to co-ordinate joint motion can be illustrated by predicting the mechanical consequences of heterogenic reflex action among the members of the triceps surae group. The soleus muscle and the heads of gastrocnemius interact reflexly as mutual synergists except for the selective suppression of the responses of soleus at moderate to high extensor forces. Soleus is a single-joint muscle which participates in determining the stiffness of the ankle joint. Gastrocnemius is a biarticular muscle with a larger moment arm at the ankle than at the knee (Goslow et al. 1973). It therefore contributes importantly to the stiffness of the ankle but acts as a dynamic link between the ankle and knee joints as well and promotes interjoint co-ordination. Since muscle torque decreases at the extremes of joint motion, it is advantageous to maintain joints in the intermediate ranges of motion. Interjoint co-ordination is therefore important to prevent any one joint from undergoing an excessively large displacement during limb movement. The kinematic analysis of joint motions in the freely moving cat of Goslow et al. (1973) shows that the knee and ankle undergo displacements which are centred around an approximately 100 deg angle during the stance phase of the step cycle independently of the size of the excursion or the speed of locomotion. It has been proposed that heterogenic reflexes contribute to the observed interjoint co-ordination under the

13 HETEROGENIC REFLEXES IN DECEREBRA TE CA TS appropriate conditions by enhancing the relative contributions of biarticular muscles to resultant limb stiffness (Nichols, 1987 b). The higher degree of coupling of joint motion occurs at higher forces where flexibility may be sacrificed for stability. This prediction concerning the co-ordination of uniarticular and biarticular muscles by heterogenic reflex action is supported indirectly by observations of muscle activation patterns to mechanical disturbances in intact cats (Abraham & Loeb, 1986). During quiet standing, a tap applied to the paw of a cat's hindlimb evoked a reflex response in both soleus and LG. On impact after a drop from a height, however, the initial brief response of LG, MG and soleus was followed by a suppression of the response of soleus. Activity in soleus again increased when the activities of MG and LG began to wain. The pattern of suppression of soleus has also been observed during the paw shake response (Smith, Betts, Edgerton & Zernicke, 1980) and during responses to horizontal displacements (Macpherson, Rushmer & Dunbar, 1986). These patterns of activity could have been triggered from a supraspinal source, but spinal reflex action appears to be configured to reinforce this pattern if not to produce it. It has been proposed that the slow soleus is suppressed under these circumstances so as not to impede the speed of the movement or postural adjustment (Smith et al. 1980), but this argument is not supported by the finding that contractions of soleus do not significantly slow plantar flexion by the triceps surae (Hutton & Enoka, 1986). Rather than serving as a mechanism for maximizing the velocity of movement, it is suggested that the suppression of soleus activity increases the degree of mechanical coupling of the ankle and knee joints under conditions where the stability of the hindlimb is critical, as in the stance phase of locomotion. An important conclusion from this study is that the organization of spinal reflex circuitry is dependent upon the state of activation of the muscle system and, therefore, heterogenic reflexes cannot be represented implicitly as constant multipliers of autogenic reflex gains. The network of heterogenic reflexes has an important co-ordinating role and should be represented explicitly in any model which attempts to describe the functions of the spinal cord in controlling posture and movement. 475 The author would like to thank Ms Debbie Koffler for help with analysis and programming, Mr Norman Smith for constructing some of the apparatus, Drs Z. Hasan and D. G. Stuart for comments on an earlier version of the manuscript, and Drs P. Lennard and J. Scholz for comments on the present version. The work was supported by N5S20855 and by grants from the University Research Fund and BRSG funds of Emory University REFERENCES ABRAHAM, L. D. & LOEB, G. E. (1985). The distal hindlimb musculature of the cat. Patterns of normal use. Experimental Brain Research 58, BALDISSERA, F., HULTBORN, H. & ILLERT, M. (1981). Integration in spinal neuronal systems. In Handbook of Physiology, section 1, vol. II, Motor Control, part 1, ed. BROOKS, V. B., pp Bethesda: American Physiological Society. BERKINBLIT, M. B., FELDMAN, A. G. & FUKSON, 0. I. (1986). Adaptability of innate motor patterns and motor control mechanisms. Behavioral and Brain Sciences 9,

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