closely resembling that following an antidromic impulse [Eccles and

Transcription

1 185 6I REFLEX INTERRUPTIONS OF RHYTHMIC DISCHARGE. By E. C. HOFF, H. E. HOFF AND D. SHEEHAN1. (New Haven, Conn.) (From the Laboratory of Physiology, Yale University School of Medicine.) (Received August 8, 1934.) INTRODUCTION. IN a recent publication Hoff, Hoff, Bucy and Pi-Sufner [1934] showed that a tendon jerk elicited during the repetitive discharge of a soleus motor neurone "resets" the rhythm of discharge of the unit in a manner closely resembling that following an antidromic impulse [Eccles and Hoff, 1932]. The number of such imposed discharges studied was too small to permit statistical analysis of the effect of time of occurrence of the added reflex discharge on the duration of the interval prior to the next succeeding discharge in the rhythmic series. The more complete data obtained in the present studies confirm the inferences drawn in the earlier report, and they give further support to the suggestion offered by E c cl e s [1931] that an antidromic volley arriving at the motor neurone via the axone produces an effect identical with that of a reflex discharge. In addition, the studies provide a basis for re-examination of the theory of motor neurone discharge developed by E c cle s and Hoff [1932]. METHODS. Cats were decerebrated under deep ether anaesthesia, and the right soleus muscle isolated by appropriate nerve and tendon section. The skin of the leg was denervated as completely as possible by section of the larger nerves and by an incision through the skin circumscribing the thigh. The leg was held by drills passing through the two extremities of the tibia, attached to the clamps on a Sherrington table. The tendon of soleus remained attached to its normal insertion, permitting reflex jerks 1 Rockefeller Fellow, Manchester, England.

2 186 E. C. HOFF, H. E. HOFF AND D. SHEEHAN. to be elicited by taps on the foot, thus stretching the muscle without the risk of stimulating inhibitory endings in the tendon by the tap itself. Action currents were led to a string galvanometer by means of silver silver-chloride pins which could be inserted into various parts of the muscle. With a light constant stretch single units could usually be isolated on the periphery of the muscle, though in other experiments the motor supply to the muscle was decreased by partial section of appropriate ventral roots, thus permitting registration of discharge of single units of higher threshold and more rapid rhythm. RESULTS. The rate of discharge of single units in these investigations was strictly comparable to the rates found by E ccl e s and Hoff [1932] in single units participating in the crossed extensor reflex of deafferented preparations. In the same unit variations in rate from five to twenty a second occurred, depending upon the degree of stretch. On one occasion, however, a single unit of high threshold was isolated by motor root section which showed a maximum rate of 33 per sec. and a minimum rate of These units of high threshold and rapid rate have been seen by one of us (H. E. H.) in soleus during the crossed extensor reflex, and about 10 p.c. of the records of single units obtained at random seem to be of this type. It may be that they represent the discharge of the small proportion of pale fibres found in soleus by Denny-Brown [1929]. Apart from their higher frequency the characteristics of their discharge are similar to those of slower units, and they are equally affected by interruptions of reflex as well as antidromic origin (unpublished observations). In three experiments the number of observations on the same single unit was sufficient to permit graphic representation. The interval before the action current of the reflex jerk (the "curtailed cycle"), expressed as a percentage of the average interval between two normal discharges, was plotted against the interval following the jerk (the "subsequent cycle"). In these experiments the time relations of the action currents of the motor discharge were used without correction as indications of the central events, as the earliest possible premature discharge would be conducted to the muscle at practically the normal rate. In every experiment curves so prepared (Fig. 2) showed that premature reflex discharge of a rhythmically firing motor neurone has the same effect on the rhythm as an antidromic impulse. Reflex discharges occurring at the very moment of a normal rhythmic discharge were followed by a cycle of normal duration,

3 REFLEX INTERRUPTIONS OF RHYTHMIC DISCHARGE. 187 while those elicited earlier in the rhythmic cycle were followed by subsequent cycles of greater than normal duration. A maximum cycle of times a normal cycle followed reflex discharges interposed almost immediately after a normal rhythmic discharge. -II W :~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~: i ~~~~~~~~~~~~~~~~~~~~~i' Fig. 1. The interruption of the rhythmic discharge of a single motor unit of soleus by a tendon jerk is shown. In A an only slightly premature reflex discharge is followed by an almost normal subsequent cycle. In C, D, and E the curtailed cycle becomes progressively shorter, and is accompanied by a corresponding increase in the length of the subsequent cycle. In D and E the first normal cycle after the reflex interruption is curtailed by a premature spontaneous discharge. In F (from another experiment) the size of the efferent volley has been reduced by cutting away ventral root fibres, but the effect of the tap remains the same. Vertical lines mark 40 a intervals. Spontaneous premature discharge following the first normal beat after early reflex interruptions characterized certain experiments, just as was found following early interruption by an antidromic volley. The interval subsequent to such a double discharge was equal to that following a reflex volley as early in the rhythmic cycle as the premature spontaneous discharge (Fig. 1 D and E).

4 188 E. C. HOFF, H. E. HOFF AND D. SHEEHAN. These experiments confirm the less numerous earlier observations that a vigorous tendon jerk can take place entirely unassociated with inhibition from any source. Eccles and Hoff [1932] pointed out that the presence of inhibition is revealed by a uniform elevation of the curve relating premature cycles to subsequent cycles. Curves derived from data obtained in these experiments pass without exception through the point 1-0: 1-0 showing that inhibition was not present. Tendon jerks have been obtained in rhythms as slow as five a second, and even in these very favourable circumstances inhibition could not be detected. 1*6. e *.*0 \ - ** ^ ~~~~~ Curtailed cycle Fig. 2. The effect of single reflex: discharges on the rhythm of a soleus motor neurone. Curtailed cycles a-s abscissm are plotted againt subsequent cycles as ordinates, both bein expressed as fractiorls of the average normal cycle. Refractory period. In every' exrperiment it was found that the neurone could be caused to discharge reflexly by means of the tendon tap within 8 a after a preceding rhythmic discharge (Fig. 1). The absolutelyrefractory period following the normal rhythmic discharge of a motor neurone can therefore not exrceecl 8a and is probably -somewhat shorter. Variations in rate of an individual single unit, or differences in rates of different units, had no detectable influence on the length of the least interval separating a,normal rhythmic discharge from the reflexr volley, although rates as high as 30 per see. were investigated, and variations in individual units from 5 to'20. per see. could be recorded. The refractory period following the reflex discharge of the tendon jerk was not studied.

5 REFLEX INTERRUPTIONS OF RHYTHMIC DISCHARGE. 189 The position of the reflex discharge in the rhythmic cycle was in no instance found to depend on the strength of the tap. Even with the very lightest taps, reflex discharges could be elicited early in the cycle as readily as later. DISCUSSION. The theory of rhythmic discharge. E ccles and Hoff [1932] suggested that a soleus motor neurone responding to continuous crossed stimulation by rhythmic discharge is subjected to a continuous and uniform bombardment by excitatory impulse from internuncial neurones. Each impulse adds to the effect produced by other similar impulses until threshold is reached, and discharge of the neurone occurs, accompanied by a dissipation or diminution of the "activity" of the rhythmic centre. The interval between two successive rhythmic discharges therefore represents the time required for the summation of the effects of individual excitatory impulses to reach a constant threshold intensity. To explain the increased interval following an early antidromic discharge it was suggested that the antidromic impulse discharged the neurone while the intensity of the excitatory processes (C.E.s.) was still subthreshold; consequently it was depressed to a lower level than following normal discharge, and a longer than normal interval elapsed before it again reached threshold intensity. It might be expected, however, that the excitation from the tendon tap would sum with the excitation from the stretch background and raise the intensity of C.E.S. to threshold, the ensuing discharge would then depress the C.E.S. to a normal level, and the subsequent cycle would always be equal to a normal cycle no matter when the "curtailed cycle" was interrupted. Since this is clearly not the case, a re-examination of the theoretical conclusions of E c c 1 e s and Hoff becomes necessary. It is possible to consider at least two alternative views. On one hand it might be that the rhythmic discharge of a motor neurone is not entirely determined by the summation of excitation to a constant threshold value, but that alterations in threshold are involved, such as are to be expected during the relatively refractory period in any excitable tissue. Little information exists concerning the relatively refractory period in neurones of the spinal cord, although Eccles and Hoff [1932] found evidence for a fairly long relatively refractory period in the motor neurone, and Hughes and Gasser [1934] observed long relatively refractory periods in internuncial neurones. It is therefore possible that discharge of a motor neurone occurs at the moment the rising intensity of excitation meets the falling threshold of

6 190 E. C. HOFF, H. E. HOFF AND D. SHEEHAN. the relatively refractory phase. If it were postulated that following a premature discharge the relatively refractory period were prolonged, an explanation would be had of the lengthened intervals following early interruption. In such an explanation the nature of the factor producing the discharge, whether antidromic or reflex, would be of no importance. A much similar explanation of the rhythmic discharge of sense organs is proposed by Matthews [1933]. Such a hypothesis could not, however, explain the very long absolutely refractory periods found in some experiments by E c cle s and Hoff [1932], which were entirely unrelated to the period of discharge. In addition, the refractory period following premature extrasystoles in cardiac tissue has been found repeatedly to be shorter rather than longer than normal [Eccles and Hoff, 1934]. It is thus unlikely that an increase in the absolutely or relatively refractory period could be the cause of the lengthened cycle following the premature interruption of a rhythmic process. On the other hand, the observed facts are susceptible of another explanation. Normally in the stretch reflex, discharge of a motor neurone results from the summated effects of the discharge of a large number of terminal fibres ending on dendrites and the cell body of the neurone. The existence of such terminals or "boutons terminaux" has been demonstrated, and their synaptic nature proven by one of us [E. C. Hoff, 1932]. The discharge of any single bouton is probably insufficient to cause more than a local disturbance, and only when a relatively large number have discharged does their combined effect reach threshold. The site of such summation may be, as has been suggested, the cell body. In the tendon jerk, however, large numbers of boutons must discharge simultaneously, and it is possible that at some region of the cell, perhaps on a dendrite, this discharge involves several boutons lying close together. Such an involvement of a larger area of the dendrite might be similar to the increase of electrode size in Gelfan's [1931] experiments, and set up a propagated disturbance which would pass down the dendrite to the cell body. On arrival there it would have an effect on the summated activity of the cell as a whole, identical with that of an antidromic impulse conducted to the cell body via the axon. If this be the case it suggests that a neurone may be caused to discharge in two ways: first by the summation of the effect produced by discharge of individual boutons on various parts of the cell as well as the repetitive discharge of the sa.me boutons; and second, by the concentrated discharge of a few boutons lying close together on a dendrite which may give rise to a propagated discharge which

7 REFLEX INTERRUPTIONS OF RHYTHMIC DISCHARGE. 191 will be conducted to the cell and cause its discharge. It may well be that very long dendrites, both in the cord and the brain, whose length seemingly makes it improbable that subliminal stimulus at the distal end could have any effect on the cell, function in this manner. SUMMARY. 1. Rhythmically discharging soleus motor neurones may be interrupted at any phase of their cycle of discharge, except during an absolutely refractory period of less than 8-10a, by the reflex discharge produced by a tendon tap. 2. Such an imposed reflex discharge "resets" the rhythm of the motor neurones so that the interval following the jerk is as long as, or slightly longer, than a normal cycle, depending on its position in the rhythmic cycle it interrupts. 3. The effect upon the rhythm of a discharging motor neurone produced by a reflex jerk is in every way identical with the effect upon similar rhythms of an antidromic volley. 4. The tension produced by the tap or by the reflex jerk was in these experiments insufficient to stimulate inhibitory endings. 5. It is suggested that in addition to discharge brought about by summation of impulses from widely separated points on the cell, the motor neurone may be activated by a propagated disturbance originating from a small area of intense stimulation. REFERENCES. Denny-Brown, D. E. (1929). Proc. Roy. Soc. Lond. B, 104, 371. Eccles, J. C. (1931). Ibid. B, 107, 511. Eccles, J. C. and Hoff, H. E. (1932). Ibid. B, 110, 483. Eccles, J. C. and Hoff, H. E. (1934). Ibid. B, 115, 307. Gelfan, S. (1931). Amer. J. Physiol. 96, 16. Hoff, E. C. (1932). Proc. Roy. Soc. Lond. B, 111, 175. Hoff,H.E.,Hoff,E.C.,Bucy,P.C.andPi-Sufier,J.(1934). Amer.J.Phy3iol.109, 123. Hughes, J. and Gasser, H. S. (1934). Ibid. 108, 307. Matthews, B. C. H. (1933). J. Physiol. 78, 1.