Mr C. J. O'NEILL of this laboratory to apply and release stretch. RucH, 1932) dealt with the single-shock crossed extensor reflex; in

Transcription

1 EXTENSOR REFLEXES OF THE CHRONIC SPINAL CAT. By K. MATTHES and T. C. RUCH. From the Department of Physiology, Oxford. (With five figures in the text.) (Received for publication 25th July 1932.) IN the acute spinal cat a crossed extensor reflex from tetanic stimulation may be totally wanting. In the chronic spinal preparation the reflex is almost always obtainable. A previous paper (MATTHES and RucH, 1932) dealt with the single-shock crossed extensor reflex; in the present paper, observations on repetitive stimulation are also recorded. METHOD. The animals (cats) were made spinal 6-79 days before myographic examination. The spinal cord was transected at a low thoracic level, aseptically and under full ether anaesthesia. All records were made with "frictionless" optical isometric myographs from soleus muscle rigidly fixed by drills through both heads of tibia and fibula. The muscle was isolated and freed by extensive nerve- and tendon-resection. The stimulating circuit was arranged to permit alternation between single and repetitive stimulation from the same induction coil (coreless and fed with two volts). For myotatic reflexes, stretch was applied to the muscle by a fall-table designed for Professor SHERRINGTON by Mr C. J. O'NEILL of this laboratory to apply and release stretch automatically. RESULTS. Plateau Tension.-An attempt has been made to record from each preparation the maximal crossed extensor response of which it is capable, and then to determine under the same conditions of initial tension, temperature, etc., the maximal motor tetanus tension of the recording muscle. In no case has the tension developed reflexly been equal to that of the maximal activation of all the motor-units making up the muscle. The ratio of maximal reflex to maximal motor tetanus tension has with great uniformity reached a value between 70 and 85 per cent. This ratio is not far below that for the chronic spinal ipsilateral reflex of tibialis anticus (FULTON and SHERRINGTON, 1932) in the same animal, i.e. cat. We have found the spinal crossed extensor

2 2 22e Alatthes and Ruch reflex gives a smaller "fraction than the reflex of tib ialis aiticus from ipsilateral popliteal nerve in the same chronic preparations. The latter is sometimes above 90 per cent. Character of Recruitment and After-contraction.-Although the variations in the character of this crossed extensor reflex are extreme, four type-reflexes can be distinguished on the basis of isometric myographic form, particularly of the ascent. In the first type there is a rapidly ascendiing reflex contraction of considerable magnitude, reaching 9() per cent. contraction within a. The ascent is definitely convex upwardis, anid after a short initial foot it approximates to a '"quadrant of a circle (GRAHAM BROWN, 1912a). This form develops its con1- traction with a rapidity equal to a good decerebrate preparatioin 0L.O pr X I I 0 7 '.4 21 sec. Fi-. L. Crosse(d extensor reflexes of soleus in 28-day spinal cat. A, repetitive stimuilation betwn-een s and s' of contralateral whole seiatic at 14 cm. (type 2). B, same, 10 cm. coil strength (approaches to type 4 of text). C is a single-shock reflex of same stimultus strength as A. D is ascent and plateau height of imiaximal ImlotoI- tetanuts. Dcafferente(l Imullscle. (ECCLES and (GRANTT, 1929). The second and more comnmnon variety (A, fig. 1) ascends to its plateau in a slow, irregular, approximately linear rise, lasting for seconds. Like the first type it usually reaches a high plateau tension. Not infrequently the recruitment opeins with anl abrupt initial step both in de-afferented and in afferented muscles. Relaxation sets in quickly, rivalling the motor tetanus when allowance for latency is made. Prolonged after-contraction of the order described for the decerebrate reflex both before (SHERRINGTON, 1909) and after de-afferentation (RANsoN, HINSEY, and TAYLOR, 1929) is abseint even in chronic spinal preparations of long standing, although the lattel possess active proprioceptive reflexes. In fact, relaxation often sets in and proceeds with a precipitancy which suggests the action of conicealed inhibition. In only one preparation has reflex contraction greatly outlasted stimulation. Spinality of the crossed extensor reflex in chronic animals is shown

3 Extensor Reflexes of the Chronic Spinal Cat 223 less in the number of motor-units excited than in the time required for their engagement and in the ability to maintain them in contraction after cessation of stimulation (SHERRINGTON, 1910). Occasionally the reflex response to contralateral stimulation is restricted to an initial twitch-like contraction of small tension which passes off leaving the muscle quiescent for the remainder of the stimulation period. There is sometimes a post-stimulation contraction. This form resembles a type of tetanic flexion-reflex described by COOPE,R, DENNY-BROWN, and SHERRINGTON (1927) under the term "jet-reflex." Finally, in some preparations stimulation of almost all intensities failed to evoke any response during stimulation. A large, irregular, and persistent contraction following on the end of the stimulus, and interpretable as "rebound" contraction, is the only sign of crossed extension (type 4) in most preparations from excessively strong stimulation. Fig. 1 contains an approach to this type. In general two or more of these forms, excepting the first variety, can be evoked in the same preparation. Stimulus intensity is an important factor, weak stimuli often producing more contraction than strong ones, which evoke the fourth type. Single compared with Repetitive Stimulation.-Single-shock crossed extensor reflexes have been recorded immediately before and after each of the tetanic reflexes described above with approximately the same stimulus intensity and without change of the conditions under which the muscle was contracting. At almost all intensities the single-shock stimulus is individually more effective for contraction when unrepeated than when repeated in a tetanic series. The most extreme instance is provided by a stimulus adjusted to give the type 4 phenomenon. Despite failure of tetanic stimulation to evoke reflex response except rebound, a single break-shock of the same intensity regularly calls forth ample reflex contraction. In less degree the same phenomenon exists for all types of crossed reflex: The gradual and prolonged recruitment of type 2 (fig. 1) typically reaches a tension equal to the single-shock reflex only after recruiting for a period considerably longer than the duration of the single-shock reflex. As in fig. 1, recruitment is frequently opened by an abrupt initial step, but the excitatory process is checked momentarily, to proceed at a greatly lowered rate. The initial step is usually not so great as an isolated single-shock reflex. It is only in the reflexes of steepest ascent that the initial segment of the ascent resembles the single-shock reflex. Rarely has a preparation been met in which single shocks were ineffective and tetanic stimulation effective. Very weak stimuli probably always gain more by repetition than do strong ones, though type 3 often occurs with quite weak stimulation. In short, throughout a considerable range of intensity, single shocks usually show some excess of reflex effect over the first shocks of a tetanus, and in some instances are of approximately equal or of even

4 Matthes and Ruch greater potency than a whole period of tetanic stimulation of the samle physical intensity. In the chronic spinal cat the crossed extensor reflex, when tetanic. seems to show, in four degrees of intensity, a self-destructive or inhibitory component. Absent largely in the first type, it shows itself in the second by a retarded recruitment after a strong twitch-like initial step, in the third by failure of contraction to be maintained throughout the stimulation period, and in the last by complete cancellation of all reflex response. The existence of afferent fibres with an inhibitory action on contralateral extensor motoneurones has been abundantly proved (GRAHAM BROWN, 1912a; GRAHAM BROWN and SHERRINGTON. 1912; ECCLES and G-RANIT, 1929; PI-SUNER and FULTON, 1929; HINSEY, RANSON, and DOLES, 1930). But the evidence of inhibition in tetanic reflexes and its seeming absence from single-shock reflexes must be due to different time relations in the genesis of crossed excitation and crossed inhibition. Analogous behaviour of ipsilateral reflexes strengthens the latter supposition. The experiments of FORBES and co-workers (1928) and ECCLES and SHERRINGTON (1931) show the existence of post-excitatory inhibition in the response to a single ipsilateral stimulus, this inhibitory appendage being capable of suppressing to some degree flexion from a second afferent volley falling several tenths of a second later. SHERRINGTON and SOWTON (1911) and BREMER (1931) find in ipsilateral extensor reflexes a masked inhibitory component of later onset than the excitatory component. We are led to conclude that an excitatory component in the crossed volley takes effect first, and that an inhibitory component developing its effect somewhat later accounts for the retardation or absence of further growth of the reflex tetanus. There remains to be explained the failure of the first shock of a tetanus to exert a reflex effect equal to that which follows the same shock when given alone. It is difficult to escape the conclusion that there is a backward-acting as well as a forward-acting interplay between inhibitory and excitatory components when the volleys are more than one. Provisionally this may be thought of as occurring during the latent period at some point of delay in the reflex arc wrhere summation (necessarily differential summation in point of time) occurs. Also it is possible that the crossed extensor "reflex twitch" (MATTHES and RUCH, 1932) represents a truncation of reflex discharge by delayed inhibitory impulses from the same afferent vollev. The long latent period of the spinal tetanic reflex equally with its slow ascent illustrates the "'inertia " of crossed extensor reflexes. More than two seconds have been observed to precede an ample, though slowly gained, plateau tension. Summation of excitation from one volley with that of a volley two seconds earlier seems improbable. On the other hand, the latent period may be occupied in a conflict of

5 Extensor Reflexes of the Chronic Spinal Cat 225 excitation and inhibition which results finally in the central excitatory state reaching the threshold for discharge. A conclusion which seems to meet these data is that the prolonged ascent of the chronic spinal-crossed extensor reflex is neither wholly the result of a slow summation of central excitation spreading over the pool of motoneurones (LIDDELL and SHERRINGTON, 1923, a and b) and increasing the frequency of discharge in each, nor the overcoming of autogeneous inhibition (SHERRINGTON, 1909; FULTON and LIDDELL, 1925; PI-SUNkR and FULTON, 1929), but is in measure a running fight between excitatory and inhibitory impulses of the same afferent volley, in which sometimes excitation and sometimes inhibition is the victor. While no systematic comparisons have been made of decerebrate singleshock and tetanic-crossed extensor reflexes, our observations prompt the suggestion that the recruiting ascent may there be in some degree impressed upon the reflex by the "mixed" character of the afferent influx. Reflex "Stepping" in Chronic Spinal Animals.-Reflex "stepping" is a spinal process (SHERRINGTON, 1906, 1910; GRAHAM BROWN, 1911; RANSON and HINSEY, 1930, a and b, etc.). In the chronic spinal cat slight "spontaneous" stepping, the "mark-time" reflex (SHERRINGTON, 1906), is seen when the cat is suspended from its forelimbs. Exceptionally in chronic spinal preparations a rhythmical reflex replaces the usual types of crossed response in soleus when a bared afferent nerve is stimulated. For example, in a fourteen-day spinal cat with section at the 8-9th thoracic segment, no adjustment of stimulus intensity would produce a smoothly sustained contraction of soleus. The reflex was always of rhythmical, step-like character, of which figs. 2 and 3 are examples. The maximum tension reached was 60 per cent. of the maximal motor tetanus. Stepping from stimulation of a single afferent nerve can be brought under the same interpretation as the similar stepping evoked by concurrent stimulation of two symmetrical afferent nerves (right and left) (GRAHAM BROWN, 1912b; SHERRINGTON, 1913, a and b). That is, a balance of inhibition and excitation on each half-centre so produced is subject to periodic alternations mediated by intracentral factors akin to fatigue and successive induction (SHERRINGTON, 1910). GRAHAM BROWN (1914) regards the rhythm as intrinsic. The crossed extensor reflex of chronic spinal animals shows in all phases the presence of inhibition. Slight changes of stimulus strength alter the proportions of inhibition and excitation to increase or annul reflex response. Fig. 2 shows the result of stimulating successively at three intensities a preparation disposed towards "stepping." Fig. 3 is the result of a yet stronger stimulus after running several seconds to allow the "steps" to assume plateau proportions. While rhythm is not absent with weak stimulation, it is slight, rapid, and irregular. In

6 2226 2Iatthes and Ruch the second record the "'steps ' are clearer but still superimposed on a considlerable recruiting excitatory background. When, however, the stimulus is strong, as in the third record and in fig. 3, the "steps" are larger and chisel more deeply in their relaxation into the excitatorv background. Now it has been shown above that strengthening the stimulus favours inhibition. Further, there is internal evidence of a progressive increase in contralateral inhibition between the three records, e.g. the initial response becomes successively less and the poststimulation activity greater. A certain level of inhibition is therefore favourable to stepping (SHERRINGTON, 1913, a and b). The response, 40% /- -5e FIG. 2.- Stepping '.in soluos of a 14-day spinal cat fromn tetanic stimulation of contralater-al peroneal nerve at, three dlifferent intensities, 25, 20, 15 cm. coil dlistance. Vertical lines m-iark the periodi of stimuilationi. in so far as the extensor muscle is concerned, seems essentially like those fromi bilateral nerve stimulation, except that the opposed central effects are here gained from inhibitory and excitatory afferents of one and the same nerve. Stepping is augmented when balance is approached by incr-ease(l intensity of stimulation, which no doubt brings in additional excitatory fibres as w%iell as the high threshold inhibitory fibres. If the stinitulus is strong enough to throw the balance to the side of inhibition, as in the third record, stepping is unfolded only after the stimulus hias r-un for a period and presumably reduced by some intracentral fact or. The configuration of a single " step "' in fig. 3 is consistent with steppging being a rap)id alternation between excitation and inhibition. The recguitment of each step" is abrupt, reaching 90 per cent. of its

7 Extensor Reflexes of the Chronic Spinal Cat plateau tension in about 200 a. Such rapidity of ascent is not usually encountered in crossed extensor reflexes, and must therefore mean a relative freedom from inhibition from the "mixed" afferent which so often imposes a gradual ascent on the spinal-crossed extensor reflex. The descent, on the other hand, describes a precipitous convex downwards curve, much like the relaxation from the accompanying motor tetanus. It resembles a crossed extensor reflex strongly inhibited by ipsilateral nerve stimulation. The absence of slowly declining afterdischarge suggests that a truncation of discharge by inhibition has actually occurred. The myogram, therefore, corresponds to an abrupt shift in the neural balance from preponderating excitation to preponderance of inhibition within and between each "step." The " staircase " formed by the first few " steps " is a common feature of our and other records of stepping, but seems to have received little comment. There is a momentum of excitation bridging over a period of boos 97) 400 1d l '/.s6sec FiG. 3.- " Stepping " in soleus of same experiment. The coil distance was 12 cm., and the record was made after the stimulus had been running several seconds. Vertical line marks the end of stimulation. M is a maximal motor tetanus of the same muscle. R is the reflex stepping. relaxation. The process which terminates one " step," instead of hindering ensuing excitation, seems actually to favour it. If the relaxation phase is in fact a period of inhibition, an augmentation of the next excitatory phase is what might be expected from the principle of successive induction (SHERRINGTON, 1906). The example presented here proves on the above analysis not to depart essentially from the cases in which concurrent stimulation of two symmetrical efferents (right and left) of mutually opposed effect evoke rhythmic contractions. The Stretch Reftex.-With passage of time after spinal transection, the reflex figure exhibited by the hind-limbs undergoes a change from the flexed or "crumpled" position of the first few days to full extension at knee and ankle. When the cat is placed on a surface giving good traction and the limbs carefully arranged and the cat restrained lightly though not held, the hind-limbs are seen to bear, for a few minutes, their share of the body-weight. The same observation on the spinal cat has been recently made by RANSON and HINSEY (1930, a and b); a recovery of ability to stand in the spinal dog has long been known

8 228 Matthes and Ruch (SHERRINGTON, 1910; MOORHOUSE, 1930), and has been demonstrated myographically (DENNY-BROWN and LIDDELL, 1927). In four cats, 84, 79, 38, and 28 days after transection of the spinal cord in the region of the last thoracic segment, myographic evidence was sought for the postural ability displayed in clinical tests. In quadriceps and in soleus of all but one cat the only response to slowly applied stretch was a faint tremulous contraction confined to the period of table-fall (LIDDELL and SHERRINGTON, 1924). One preparation, however, reacted reflexly to slow application of stretch to soleus. Fig. 4 shows the curve of tension (solid line) during a stretch of 5 mm. applied through a period of several seconds. To separate reflex and I, sec FIG. 4.-Spinal stretch reflex of 8oleu8 muscle. Cord section 79 days before myographic examination. The solid line (M) is the response of muscle to table-fall (T) of 5 mm. Dots (I) response of the muscle to a similar table-fall while imder strong ipsilateral inhibition between the signal marks. The maximal motor tetanus was 850 grm. passive tension resulting from the table-fall, a record was made immediately after with the same initial tension and table-fall, but with the reflex component annulled by strong pre-.and intercurrent ipsilateral inhibition. The tension developed under inhibition is a fraction of the whole stretch-reflex. This fraction was proved in latter records to be identical with the tension exerted by the muscle after severance of its motor nerve. The spinal stretch-reflex as we have observed it in the cat lacks the stability of the decerebrate stretch-reflex. All of the records show remissions of contraction (cf. SHERRINGTON, 1910) during the period of increasing stretch or " phasic " portion of the myotatic contraction. These are carried on and are intensified during the period of " static " or maintained stretch. It is in the response to static stretch that the deficiency of the isolated spinal cord is most apparent. The decerebrate reflex

9 Extensor Reflexes of the Chronic Spinal Cat 229 suffers some loss of tension during the static period, but after a short time strikes a level which can be maintained for minutes. In our records the spinal stretch-reflex is usually poorly sustained, and is often largely dissipated in the few seconds comprised within the record. In fig. 5 such rapid disintegration is shown, and is the more remarkable because the reflex tension of the phasic portion is not greatly inferior to the absolute maximum tension of which the muscle was capable (88 per cent.). The decline in tension sets in sometimes before the table M... b ab 0 / 2 3 sec FIG. 5.-Spinal stretch-reflex under same conditions as preceding figure. high peak reaches 88 per cent. of maximal motor tetanus. The early and ceases to fall. This feature peculiar to the spinal reflex may either represent an early inadequacy of proprioceptive impulses sufficient to maintain contraction, or a termination by autogenous inhibition. Yet the response of soleus muscle to stretch obtainable in some chronic spinal cats, as in the chronic spinal dog (DENNY-BROWN and LIDDELL, 1927), proves the stretch-reflex to have essentially a spinal element. Nevertheless it is heavily impaired by loss of nexus between spinal cord and the brain, even after allowance of weeks and months for recoverv from spinal shock. The spinal reflex seems particularly inadequate in maintaining motor units in contraction once engaged.

10 230 Matthes and Ruch SUMMARY AND CONCLUSIONS. 1. The fraction of the maximum tension capacity of m. soleus which can be enlisted in reflex contraction from a large contralateral nerve is per cent., in chronic spinal animals. 2. The rate and type of recruitment in the crossed extensor reflex of spinal animals are largely determined by the proportion of excitatory and inhibitory fibres excited by a given intensity of stimulus. 3. A single shock is a more effective stimulus to contralateral extension th an is a tetanic series of such shocks. This discrepancy increases with strong stimuli. An interpretation is offered in terms of different time relations in the development of central excitation and inhibition from the crossed nerve. 4. The "spinality" of crossed extensor reflexes is more apparent with tetanic than with single-shock stimulation. 5. Spinal "stepping" in the isolated soleus evoked by contralateral nerve-trunk stimulation of varied intensity is described, and evidence is given for interaction of excitation and inhibition as a factor in the genesis of stepping. 6. The myotatic reflex to slowly applied and to maintained stretch in chronic spinal cats usually remains scanty, despite recovery of proprioceptive arcs enabling the hind-limbs to stand. An instance of well-developed stretch-reflex in soleus muscle of a chronic spinal cat is recorded. Expenses for materials were in part met by the Rockefeller Foundation. We wish to thank Professor SHERRINGTON for his advice, and for receiving us into his laboratory. REFERENCES. (1) BREMER, F., C.R. Soc. Biol. Paris, 1931, cvi (2) BROWN, T. GRAHAM, Proc. Roy. Soc., B, 1911, lxxxiv (3) BROWN, T. GRAHAM, Quart. Journ. Exper. Physiol., 1912a, v (4) BROWN, T. GRAHAM, Proc. Roy. Soc., B, 1912b, lxxxv (5) BROWN, T. GRAHAM, Journ. Physiol., 1914, xlviii. 18. (6) BROWN, T. GRAHAM, and C. S. SHERRINGTON, Journ. Physiol., 1912, xliv (7) COOPER, S., D. E. DENNY-BROWN, and C. S. SHERRINGTON, Proc. Roy. Soc., B, 1927, ci (8) DENNY-BROWN, D. E., and E. G. T. LIDDELL, Journ. Physiol., 1927, lxiii (9) ECCLEs, J. C., and R. GRANIT, Journ. Physiol., 1929, lxvii. 97. (10) ECCLEs, J. C., and C. S. SHERRINGTON, Proc. Roy. Soc., B, 1931, cvii. 535.

11 Extensor Reflexes of the Chronic Spinal Cat (11) FORBES, A., A. QUERIDO, L. R. WHITAKER, and L. M. HURXTHAL, Amer. Journ. Physiol., 1928, lxxxv (12) FULTON, J. F., and E. G. T. LIDDELL, Proc. Roy. Soc., B, 1925, xcviii (13) FULTON, J. F., and C. S. SHERRINGTON, Journ. Physiol., 1932, lxxv. 17. (14) HINSEY, J. C., S. W. RANSON, and E. A. DOLES, Amer. Journ. Physiol., 1930, xcv (15) LIDDELL, E. G. T., and C. S. SHERRINGTON, Proc. Roy. Soc., B, 1923a, xcv (16) LIDDELL, E. G. T., and C. S. SHERRINGTON, ibid., 1923b, xcv (17) LIDDELL, E. G. T., and C. S. SHERRINGTON, ibid., 1924, xcvi (18) MATTHES, K., and T. C. RumC, Journ. Physiol., 1932; in the press. (19) MooRHousE, V. H. K., Amer. Journ. Physiol., 1930, xcii (20) PI-SUNER, J., and J. F. FULTON, Amer. Journ. Physiol., 1929, lxxxviii (21) RANsoN, S. W., and J. C. HINSEY, Proc. Soc. Exper. Biol., N.Y., 1930a, xxvii (22) RANSON, S. W., and J. C. HINSEY, Amer. Journ. Physiol., 1930b, xciv (23) RANSON, S. W., J. C. HINSEY, and L. A. TAYLOR, Amer. Journ. Physiol., 1929, lxxxviii. 52. (24) SHERRINGTON, C. S., " The Integrative Action of the Nervous System," London, (25) SHERRINGTON, C. S., Quart. Journ. Exper. Physiol., 1909, ii (26) SHERRINGTON, C. S., Journ. Physiol., 1910, xl. 28. (27) SHERRINGTON, C. S., Proc. Roy. Soc., B, 1913a, lxxxvi (28) SHERRINGTON, C. S., Journ. Physiol., 1913b, xlvii (29) SEERRINGTON, C. S., and S. C. M. SOWTON, Proc. Roy. Soc., B, 1911, lxxxiii VOL XXII., NO