Principles of General Physiology

The simplest of these mechanisms is that in which two neurones only are concerned : the receptor neurone, whose cell body is outside the nerve centre, and the motor neurone, whose cell body is within the nervous centre, but whose long nerve fibre, or axone, passes out to some peripheral effector organ, such as a muscle. This is a reflex arc, in which a sensory impression gives rise to a motor response. It is the functional unit of the nervous system, as the neurone is its anatomical one.

Even as low as the earthworm, a new set of neurones is to be found, association neurones, which lie entirely within the central nervous system. These serve to connect the neurones of one segment with those of other segments ; although, in this case, they rarely extend beyond two segments. The progress of the nervous centres in complexity and efficiency of integration depends essentially on the formation of longer and longer association neurones. These form, as it were, loops, consisting often of several neurones, which extend further and further from the original simple arc of two neurones, so that the most highly developed parts of the system, such as the cerebral cortex of the higher vertebrates, consist of association neurones only.

The neurone itself, as a cell, possesses the general properties of protoplasm. The cell body, containing the nucleus, consists of a viscous fluid, with numerous very fine granules in suspension. In life, there is no evidence of the presence of Nissl bodies or neuro-fibrils, and there is every reason to suppose that they are artefacts, as we see them in fixed preparations, although the substance out of which they are formed must have been present in the living cells.

The mode of embryological growth of nerve fibres from cells suggests aimeboid movement. Whether this is still present in the adult cell is uncertain, although possible. The protoplasm itself does not seem to be essential for conduction of impulses serving for reflexes, but probably acts as a means of reinforcing the strength of disturbances and certainly, with its nucleus, acts as the nutritive centre of the neurone. Owing to the protoplasmic nature of the cell bodies, nerve centres are very sensitive to deprivation of oxygen. No metabolic process other than oxidation, with evolution of carbon dioxide, has been shown to be present in the normal activity of nerve centres.

A true nerve network, with central functions, such as that of reflex action, does not appear to exist outside of the very simplest types of nervous system. The plexuses of distribution of the nerves to smooth muscle and related structures serve only for conduction, not for initiation of impulses. The properties of the synaptic membrane are of great importance. Such properties of membranes as those described in the earlier chapters of this book must be shown by it. The phenomena of fatigue, summation, irreciprocal conduction, excitation and inhibition are connected with this membrane.

The use of one motor neurone by several receptors, brought about by the existence of these modifiable synaptic membranes, enables great economy and integrative efficiency to be obtained. This is the principle of the " final common path " of Sherrington. Although, in rare instances, a reflex arc may consist of two neurones only, receptor and motor, in the great majority of cases at least three are present, the additional one being a longer or shorter association neurone. The whole of the arc, with the exception of the motor neurone (final common path), may, for convenience, be called the afferent arc.

The cerebral ganglion, or brain, is developed in the anterior end, or head, of an animal in connection with the formation of the elaborate system of the " distance receptors," which enable the organism to take account of occurrences not in immediate contact with it. The reactions of the highest part, the cortex cerebri, show, in contradistinction to the reflexes of the spinal cord, much greater possibilities of modification by events elsewhere and by previous activity. Inhibitory phenomena are especially noticeable and the power of changing excitation into inhibition, and vice versa, is a characteristic function of the cortex. Other properties are discussed in the text.

Certain aspects of the formation of new associations, or " memory," are also discussed in the text. The sympathetic system, as well as the autonomic or visceral system in general, is not an independent nervous system, but an outflow or outflows of efferent fibres from particular regions of the central nervous system. Its characteristic is the presence of synapses with secondary neurones, either in the sympathetic chain, or more peripherally ; the axones of these second neurones are non-medullated. The visceral system develops by outgrowths of chains of cells, whereas the somatic system is formed by outgrowth of axones from cells in the centres.

Auerbach's plexus, although endowed with reflex functions, is also developed as an outgrowth from the central nervous system and cannot be regarded as » survival of a primitive peripheral nervous system. As pointed out in the preceding chapter, the reflex is to be regarded as the functional unit of the nervous mechanism. Its general nature was described in that place. In exceptional cases, such as the knee-jerk, the reflex arc may, apparently, consist of two neurones only, but, as a general rule, three at least are contained in it, as in the scratch reflex.

For the investigation of the characteristic properties of the spinal reflexes, it is clearly necessary to obtain a preparation in which the spinal cord is separated from the higher centres and has recovered from shock. Such an animal is called by Sherrington the spinal animal, and it is by his work that the possibility of maintaining such animals alive and healthy has been demonstrated. Nearly all the results to be described below are due to Sherrington, whose portrait will be found in Fig. 150.

Sherrington then sums up the chief differences between conduction in nerve trunks and in reflex arcs as follows (1906, p. 14): "Conduction in reflex arcs exhibits (1) slower speed as measured by the latent period between application of stimulus and appearance of end-effect, this difference being greater for weak stimuli than for strong ; (2) less close correspondence between the moment of cessation of stimulus and the moment of cessation of end-effect, i.e., there is a marked 'after-discharge'; (3) less close correspondence between rhythm of stimulus and rhythm of end-effect ; (4) less close correspondence between the grading of intensity of the stimulus and the grading of intensity of the end-effect ; (5) considerable resistance to passage of a single nerve impulse, but a resistance easily forced by a succession of impulses (temporal summation) ; (6) irreversibility of direction instead of reversibility as in nerve trunks ; (7) fatigability in contrast with the comparative unfatigability of nerve trunks ; (8) much greater variability of the threshold value of stimulus than in nerve trunk ; (9) refractory period, ' bahnung ' (or facilitation), inhibition and shock, in degrees unknown for nerve trunks; (10) much greater dependence on blood-circulation, oxygen (Verworn, Winterstein, von Baeyer, etc.); (11) much greater susceptibility to various drugs, anaesthetics."

These differences are obviously due to the passage through synaptic junctions; perhaps, in some cases, passage through the cytoplasm of the cell body of some constituent neurone may play a part. Latent Period. — The measurements of Jolly (1910) in the case of the flexion reflex and the knee-jerk have been given on page 476 above. The more intense the stimulus, the shorter the latent period, so that with intense stimuli to the afferent nerve, the delay may scarcely exceed that of the conduction along the nerve trunks alone. The difference between strong and weak stimulation may amount to as much as ten times or more. This delay might be due to the time occupied in setting the synapse into a state of capability of transmission, but experiments by Sherrington (1906, p. 24) did not support this view. A reflex was evoked by a weak stimulus, with a certain latency ; the strength of the stimulus was then suddenly increased, and the latent

period compared with that of the reflex evoked by the same strong stimulus when applied as an initial one. In the first case, the synapse had been already prepared, in the latter case, not. The latent period was, indeed, a little shorter in the former case, but not sufficiently so to give any support to the view mentioned. The delay must, therefore, be chiefly in the actual transmission, and not in making the synapse conductive, nor in an amoeboid movement of protoplasmic processes into contact with each other.

Incidentally, the fact shows the importance of the cutting off by inhibition of impulses which are not wanted, since the channels to the final common path on the efferent side seem to be always open ; no preparation is needed. The latent time of a reflex inhibition is no longer than that of an excitation. After-Discharge. — The discharge from a reflex arc does not, as a rule, cease when the stimulus ceases, often lasting for five seconds or more. The duration is proportional to the intensity of the stimulus. With a weak stimulus, the response may not appear at all until after the actual period of stimulation has passed.

The after-discharge can be cut short sharply by an inhibitory influence, as shown in Fig. 107 (page 388). This rapid arrest is an arrangement for successive interchange of reflexes. It prepares the neurone for another stimulation. Summation. — A 1- though, as we have seen, there is a phenomenon of this kind to be met with in the case of nerve itself, it is of a limited kind compared with that shown by reflexes. A scratch reflex cannot be elicited by a single induction shock, however strong. On the other hand, very feeble shocks, if they follow one another at not too short intervals, sooner or later evoke a response. In one case, no effect was produced until after forty-four shocks at eighteen per second had been applied to the skin.

The flexion reflex, that is flexion of the knee produced by nocuous or electrical stimulation of the skin of the foot, differs from nearly all other reflexes by being elicitable by a single shock. Facilitation. — This word is used by.Sherrington as a translation of " Bahnung." One aspect of the phenomenon is the summation mentioned in the preceding paragraph. It is also to be seen in the fact that when a reflex produced from two different receptors employs the same final common path, simultaneous application of stimuli to both receptors evokes a larger response than if applied to either alone. This may also be called " reinforcement," and plays an important part in the behaviour of an organism to the various stimuli playing upon it at one time. These combinations of stimuli form, as Sherrington puts it, "constellations of stimuli." It must also be remembered that a reflex not only takes possession of

FIG. 151. SUMMATION EFFECT (IMMEDIATE SPINAL INDUCTION) BETWEEN THE ARCS So,, Signal marking period of stimulation of the skin belonging to arc R& of the shoulder skin. The strength of the stimulus is subminimal, so that there is no reflex res)>onse. S/3, Signal marking stimulation, also subminimal, of a point of the shoulder skin 8 cm. from ./fa. Though the two stimuli applied separately are each unable to evoke the reflex, when applied conU'inix r-

The two arcs Tfci and Rfl, .therefore, reinforce each other in their action on the final common ]>ath, FC. Time in fifths of seconds. Read from left to right certain final common paths, but also of those whose muscles would oppose those of the reflex itself. It inhibits the opposing neurones from being set into action by other reflexes at the same time. Induction. — Closely allied to the preceding are the phenomena of induction. If the receptive skin area for the scratch reflex is stimulated at one point with subminimal intensity, a reaction may be evoked if another point in the same area be stimulated at the same time, also with subminimal intensity. Such reinforcement is called by Sherrington (1906, p. 120), immediate spinal induction (see Fig. 151). It appears that both stimuli act on the same set of neurones composing

the final common path, and, indeed, on the whole of the motor neurones of which it consists. This is shown by the fact that two weak stimuli may be made to alternate with each other, each stimulus of the one coming between those of the other. If they acted on different neurones, signs of two rhythms should appear in the muscles of the leg. There is not even a break or interference in the rhythm of the first reflex when the second is added, although the amplitude may be increased. The result must be due to the refractory state induced by each of the first series of stimuli, and in the same neurones (see Fig. 152).

This immediate induction only occurs between allied reflexes, which will be referred to again later. Successive Induction, on the other hand, is of a different nature. Suppose that we excite an extension reflex in one leg by appropriate stimulation of the opposite leg and with such a strength of stimulus that the reflex is a small one. This is done at regular intervals and the reflex is found to be very constant. In one of the intervals, a strong and prolonged flexion reflex is excited from the limb itself. After this, the extension reflexes are increased both in height and in duration, the effect gradually passing off (Fig. 153). During the flexion reflex, the extension arcs were inhibited and the phenomenon is the same as the "rebound," referred to under the head of inhibition above (page 422). This exaltation, after a period of inhibition, is not shown by merely removing the exciting stimulus, so that it is not due to rest.

It will be clear that the increased excitability produced by one reflex for its antagonist reflex plays a part in the mechanism of such alternating movements as those of stepping or locomotion. Irreversibility of Direction. — It is a wellestablished fact that nerve fibres conduct in both directions.. The experiments of Bell and Majendie showed, however, that stimulation of the spinal end of a motor root gives no sign of reflex nor of sensation. Similar results of Gotch and Horsley have been mentioned above (page 475).

The experiments of Veszi (1909) showed that fatigue of the reflex mechanism could not be obtained by stimulation of the axones of the motor neurones, and those of Fro'hlich (1909, 2) showed that the same thing applies to the simple reflex arc of the stellar ganglion of the Cephalopod. While fatigue of this ganglion can readily be produced by stimulation of the nerves proceeding to it from the cerebral mass, it cannot be fatigued by stimulation of the motor nerves which it gives off to the muscles of the mantle.

We have seen when discussing the properties of the true nerve network of Medusae that excitation passes in all directions. It appears from fixed preparations that the " neuro-fibrils " are, in this case, continuous from one cell to another, and, although these are probably artefacts, the fact of their continuity suggests Scratch reflex elicited from two skin points, A and B. The point A gave the "low" form of reflex ; B the " high " form. The interval between the stimuli at B much shorter than at A. The slow rate at A is marked between the signal lines.

Note the absence of any sign of interference of rhythm when the second series of stimuli comes in and when the first is cut off. Hence all the neurones of the final common path must have been active in both cases. that the substance from which they arise is continuous and nob broken by a synapse, as in the higher forms of " polarised " nerve centres. It would be premature to attempt an explanation of why the synaptic membrane is permeable to excitation in one direction only. It may be that it is permeable to one ion only of an electrolytically dissociated colloid, in the way described on page 141 for the system of Congo-red and parchment paper. In such cases, an electrical current can only pass in one direction. But further knowledge is needed.

Refractory Phase, — This characteristic property of muscle and of nerve trunks has been described above. In many reflexes, such as the scratch reflex, it is FIG. 154. RECIPROCAL INNERVATION OF THE EYE MUSCLES, ACCORDING TO DESCARTES. — Gutschoven's sketch to illustrate Descartes' description. very marked. This reflex consists of alternate flexion and extension at a rate of about four times per second. This rate is independent of the frequency of the stimulation, so that it is the same when the stimulus is a constant current. High-frequency currents are also very effective (Sherrington, 1906, pp. 48 and 49). Alteration in strength of stimulus has no effect on the rate of discharge. Suppose that the stimuli are applied at the rate of one hundred shocks per second, it is clear that the greater number of these must be ineffective ; in other words, they fall in a refractory period.

We have already seen that the reflex arc in this case consists of at least three neurones, in addition to the muscle fibre at one end and the receptor organs in the skin at the other end. Where in this series are we to place the seat of the refractory period ? Now, when the motor neurones, made use of by this reflex, are excited for a different reflex from receptors in the leg itself, this refractory phase does not show itself ; the flexion reflex is a steady one. We can exclude, therefore, the motor neurones of the final common path, as well as the muscles themselves. We have seen above that there must be some mechanism common to impulses started at two different spots in the receptive area, even when they are 10 cm. apart. There is, further, no evidence that there is any direct connection between receptor neurones themselves ; there is only that due to their

synapses with other neurones common to both receptors. The conclusion is that the refractory period must be in some neurones on the afferent side of the motor neurones of the final common path, a conclusion which, indeed, seems to be necessary for the proper working of the reflex mechanisms; since the rhythmic movement of scratching would not do for the other reflexes in which the same motor neurones take part. It is interesting to note that the rate of the rhythm is almost identical with that observed by Gotch and Burch (1896) in the discharge of the electrical cell of Malapterurus.

When there arc two sets of muscles acting on a movable organ, such as the eye or a part of a limb, in such a way that they antagonise one another, it is clear lhat, for the effective performance of a particular reflex movement, any contraction of the muscles opposing this movement must be inhibited. Further, the inhibition of the one group must proceed pari passn with the excitation of the other group to ensure a well-controlled and stead}' motion.

This fact was obvious to Descartes (1677), and Figs. 154 and 155 are taken from his treatise " De THomme." The history of this work is of some interest. References are usually made to the Latin translation, " De Homine," but, happening to come into possession of an edition in French brought out by Descartes' friend and disciple, Clerselier, I wondered why the original French manuscript of the author had been translated into Latin and then, apparently, back again into French. On

investigation, I found that Descartes, having the fate of Galileo before him, was by no means desirous of offending the ecclesiastical authorities, so that the work remained unpublished at his death in 1650. Clerselier had one copy of the manuscript and another copy was translated into Latin by Schuyl and published at Leyden in 1662. Clerselier, hearing of this, hastened to publish the original French manuscript in Paris. In the second edition, of 1677, he apologises for some errors which, owing to the hurried publication of the first edition, had crept in. So that his second edition appears to be the most accurate representation of the original.