Principles of General Physiology

When reflexes use the same final common path for different purposes, they may either reinforce or inhibit each other. Even if they both excite, they may not be able to use the motor neurones at the same time, if they use them in a different way. The proprio-ceptors of a muscle are of use in cutting short one reflex and preparing the arc for another. There are numerous compound reflexes, in which the result of one sets another into play. The intermediate synapses of a reflex arc are comparatively easily fatigued, whereas the motor neurones themselves are not so. This fact is of value in preventing the occupation of a particular arc by one reflex for too long a time. Recovery is fairly rapid. A reflex may cease, therefore, either from fatigue or by inhibition, and there are differences between the two cases by which they can be recognised.

Reflexes from nocuous stimuli are prepotent. Their receptors are probably free nerve endings. The stimulus required is comparatively large, as is appropriate to the purpose of the reflex. The mechanism of autotomy in the crab is described in the text. The' difference between spinal reflexes and those in which the higher centres, and especially the cerebral cortex, take part is the regularity of the former and the ease with which the latter are modified or abolished by events in other parts of the central nervous system. For this reason, Pavlov calls the former "unconditioned " and the latter " conditioned " reflexes.

Notwithstanding this fact, Pavlov has devised methods by which conditioned reflexes are amenable to experimental investigation and obtained many valuable results. The two fundamental mechanisms involved are those of temporary association and that of the " analysers." By the former, a stimulus presented several times in conjunction with an unconditioned stimulus, such as food in the mouth, has ultimately the effect of exciting salivary secretion when presented alone. It has become a conditioned reflex and presents the opportunity for testing the effect of various other stimuli, or events in the external world, on cerebral phenomena.

The " Analysers " are the sense organs, together with their central connections. The production of a conditioned reflex may be expressed in one way by saying that the reflex arc has taken on a new afferent neurone. But it must be remembered that the connection with this neurone is very easily broken or inhibited, and is modifiable in various ways. Inhibition is, in fact, the most common fact met with, as in the experiments of Graham Brown and Sherrington on cortical stimulation, as described on page 480. It may even show itself as internal inhibition, when the proper consumma-

the,m of the conditioned reflex, that is, food, fails to be presented after a number T of repetitions of the stimulus for the conditioned reflex. Other interesting examples of inhibition will be found in the text. '^Certain forms of conditioned reflex obtain the mastery over nociceptive reflexes, contrary to the case of spinal reflexes. Thus, a painful stimulus can be made into the sign for a conditioned reflex, and then ceases to be painful. Removal of portions of the cortex affects permanently the possibility of conditioned reflexes in which these portions take part normally.

The bearing of the facts of inhibition on hypnosis and sleep is pointed out. ORGANISMS of all kinds maintain their existence by adapting themselves to changes in the world of things surrounding them. They depend upon it for their food and must avoid, or defend themselves from, other organisms which want them for food. As we have seen, nerve fibres themselves can be excited by various kinds of stimuli, chemical, electrical, mechanical, and so on. But it will be obvious that an organism is the better equipped the more delicate its sensibility to the actions of the outer world. Nerve fibres themselves, in fact, require rather powerful stimuli to excite them. Contrast, for example, the force required to stimulate a delicate organ of touch, such as the human skin, with that necessary to stimulate the trunk of the sciatic nerve of the frog.

Intra-epithelial nerve terminations in the larynx. Gplgi method. On the left, stratified epithelium. On the right, ciliated columnar epithelium, w, Nerve fibres in the corium. It is natural to suppose that stimuli of an injurious nature would be amongst the first to be responded to in the course of evolution. We noticed that there is reason to believe that free nerve endings are sufficient for the appreciation of these stimuli, since it is not desirable that a stimulus, too weak to be harmful, should evoke a reaction of flight. In fact, we actually find that free nerve endings are present in the skin (Fig. 159).

The earliest animals arose in the sea, and would naturally be exposed to a great variety of chemical substances dissolved therein. Parker (1912) finds that the skin of fish is sensitive to acid, alkali, and salts, also to quinine. It appears that it is the hydrogen and hydroxyl ion concentration of the two first which are the active properties. It requires a considerably higher concentration of sodium chloride than of hydrochloric acid to stimulate these receptors, although, in the concentrations used, both would be almost completely dissociated, and the number of chlorine ions would be proportional to the concentration. Similarly, sodium hydroxide is more powerful than sodium chloride.

We may also take note that the concentration of acid or alkali required, about 0'05 molar, is very much higher than that to which the differentiated receptors in the human tongue are sensitive. This fact suggests that it is free nerve endings that are stimulated in the fish by the irritant action of the substances named. This view is confirmed by the fact that twice molar sugar, which cannot be supposed to be nocuous, has no effect. The senses of taste and smell are higher developments of this primitive chemical sense. Delicate special receptor organs have been formed, especially in the land vertebrates. That of smell has, indeed, become a kind of distance receptor, of great importance in many animals, owing to the stimulant substance being conveyed by air or water. It might be thought that the name of smell should be confined to the appreciation of vapours, but it must be remembered that, before acting on receptors, these vapours must enter into solution in the liquid covering the receptors. There is, therefore, no sufficient reason to make a distinction between this sense in the shark and in the dog. It is obvious, however, that transmission through the air by currents is more rapid than through water, and that, for this reason, the growth of the mechanism as a distance receptor, becomes more obvious in land animals. The nature of smell as a distance receptor in fishes is discussedby Parker and Sheldon (1913).

The sense of taste is much less delicate than that of smell, and cannot be said to play a great part in the growth of the higher nervous systems. It has scarcely any distance element, even in its most developed form. It is remarkable that, even in the higher vertebrates, the sensory neurones of smell receptors have retained their primitive condition of cell body in the epithelium itself with nerve processes passing into the central ganglion. But it seems doubtful whether this fact altogether justifies the view suggested by Parker (1912) that the sense of smell represents the ancestral chemical sense. The epithelial cells would very early form chemical products by the action of external chemical agent^, products of such a nature as to stimulate the free nerve endings between the epithelial cells and thus form a common basis front which the more delicate mechanisms of smell and taste have been developed. At the same, time, we must be careful in limiting these activities to purely chemical ones, since it is difficult to imagine any chemical property common to lead acetate, saccharin and glucose. The acid taste, apparently, is merely a question of hydrogen ion concentration, and it is not difficult to suppose the existence of some peripheral chemical substance very sensitive to this factor.

In addition to the action of chemical substances in the water surrounding them, primitive organisms are exposed to contact with other objects. Such contacts probably, at first, acted as nocuous stimuli merely, of a nature indistinguishable from one another, but evoking the powerful nociceptive reflexes. It is curious that, according to Cohnheim (1912, 2, p. 112), the molluscs known as " Heteropods " are insensitive to the presence of food until it comes into contact with them, apparently being unable to appreciate it by chemical sense or by vision, although they possess eyes. After biting an object, however, they appear to recognise by taste whether it is fit for food or not.

From the varied effects produced by substances in contact with the skin, the elaborate system of skin receptors, as we know it in ourselves, has been differentiated. But before we proceed further to the consideration of the higher sense organs, and especially of the distance receptors, a few additional introductory remarks of a general nature are necessary. Organisms, as remarked above, are the better provided for their adaptation to changes in their environment, the greater the number and variety of external phenomena which they are capable of appreciating. To be aware of things happening at a distance gives opportunity for preparation to meet them before they actually arrive. Hence the great advance in animal organisation with the development of organs, such as the eye and the ear, which enable things at great distances to impress themselves.

It is also very necessary that many events occurring in the organism itself should be made known to the nerve centres. We have, as well as extero-ceptors, intero-ceptors, as they are called by Sherrington, and, amongst these, the , proprioceptors are of great importance. These are the receptors in an active organ which give information to the centres of the state of activity of this organ, and are thus the means of influencing it reflexly. We shall see the part played by these receptors in discussing " plastic tonus " in the next chapter.

An illustration may assist here. Suppose a general commanding a battle in which s. \, r,il regiments ar« engaged and extending over a wide area. It is clear that, in order that a particular movement may be effectively ordered, it is necessary for the general to know that the previous order has been carried out. The message may, perhaps, not have reached the body of troops in question. Again, since we judge of the distance between one inaccessible object and another by movement of the eyes, the centres must be made aware that the eye muscles have actually executed the movement intended ; knowledge of the sending of an efferent impulse is not sufficient of itself, for the nerve may have been unable to conduct it.

As regards the variety of external forces for which sense organs have been evolved, it is .not to be forgotten that there may be forms of energy for which we have no appropriate receptors. Moreover, it is possible that other animals than ourselves may be able to appreciate phenomena of which we are unaware. Quantitative differences of this kind are familiar. We have no appropriate receptors for ultra-violet light. The cat is able to hear notes higher in pitch than man can, and so on.

Further, a form of energy which we know by physical experiments to be one and the same, such as radiation from the sun, is known to us as light or as heat, according to the particular receptors on which it falls, although the only difference is in rate of vibration. More precisely, a particular, somewhat narrow, range of rate of vibration or wave length, appears to the eye as light, longer or shorter wave lengths are unappreciated ; but the long waves which have no effect on the retina are able to stimulate certain receptors in the skin and are then called heat.

We see thus, that, in order that a particular form of energy may be able to produce a propagated disturbance in the receptor neurone, what is necessary is that a mechanism of some sort shall be present in which changes shall be produced of sufficient magnitude to excite the nerve fibres, although the incident energy itself may be far too small to do so if it acted directly on the nerve. How small an amount of energy is able to produce such a nerve impulse, if it acts through an appropriate receptor, is shown by the calculation of V. Henri et Larguier des Bancels (1911, p. 856), who found the retina to be sensitive to an amount of light energy as small as 5 x 10~12 ergs. This is about three thousand times as sensitive as the most rapid photographic plate. These considerations naturally lead us to expect that the nature of the receptor organ will vary greatly according to the particular form of energy to be detected ; just as we use a galvanometer to detect electrical currents, a thermometer for heat, an actinometer for light, and so on. It is also instructive, in view of the facts to be considered in the next paragraph, to remember that it is possible to detect and measure all forms of energy by converting them into electric currents. Heat, by the use of a thermopile as receptor, sound by a telephone, ordinary kinetic energy by using it to turn a dynamo, chemical energy, as that of the neutralisation of a base by an acid, by the use of the hydrogen electrode, or indirectly by conversion to heat and then by the thermopile, can all be converted into electric currents in a wire, just as in our receptor organs of sense they are converted into nerve impulses.

There is, however, a difference to be noted ; in the sense organ a small incident energy is caused to set free a larger amount of energy by what we may call a " trigger " action ; as if, in our physical instruments, we always made use of what is known as a " relay," such as is done to magnify the energy of the electrical waves received in wireless telegraphy, where a minute amount of energy is caused to complete the circuit of an independent battery, and to set in action a much greater quantity of energy, which can readily be detected.

Mi/fler's Law. — -We saw in Chapter XIII. that all evidence points to the fact that there is no difference between forms of nerve disturbances. Impulses may follow one another at different rates, within the limitations of the refractory period, but the individual impulses are in all cases alike, with the single exception of those that follow immediately in the wake of a previous disturbance. Even here, the first disturbance is a normal one and those that follow only differ from it in magnitude. This being so, impulses produced in the optic nerve by light on the retina are identical with those produced by sound in the auditory nerve, by

touch in the skin nerves, and so on. It is obvious that the differences recognised by the organism must be due to "analysers" in the central nervous system. Something has already been said on this point in discussing Pavlov's conditioned reflexes (pages 503-504), and attention may be called to Fig. 158 (page 504). We meet with the phenomenon again in the form of Mliller's law of "specific energies," as he called it (1843, p. 1065). The word "energy" is unfortunate here, since it is used in the sense merely of " endowment " or " property " and Mliller himself uses it interchangeably with " quality." The law amounts to this, that, however excited, each nerve of special sense gives rise to its own peculiar sensation. Miiller also (1826, 1840, and 1843) points out that the same external cause may excite a different sensation in different sense organs. " Sensation is not a conduction of a condition of certain external bodies directly to consciousness, but the conduction of a state of a particular nerve, and the excitation of each nerve of special sense has its own peculiar sensation, which cannot be replaced by that of any other nerve."

The section in Miiller's book (1843, pp. 1059-1087), dealing with the senses in general, may be read with profit. It is probable that some of the misunderstanding of the meaning of Miiller's law is due to the fact that he sometimes speaks of "nerves" when we should now say "nerve centres." The statement on page 1072, however, that "it is certain that the central portions of the nerves, included in the encephalon, are susceptible of their peculiar sensations, independently of the more peripheral portions of the nervous cords, which form the means of communication with the external organs of sense," shows that he was fully aware of the fact that the nerve trunks act as conductors only.

The fact that sensation of light is evoked by section of the optic nerve is often brought as proof of the statement before us, but, since a slight pull on the retina very easily excites the receptors there, it is, by itself, only evidence that the mechanical stimulation of the retina, as well as that by light, can produce the special sensation. The best proof is that afforded by the trunk of the chorda tympani nerve as it passes through the tympanic cavity, as referred to above (page 388). A sensation of taste is produced by either mechanical, chemical, or electrical stimulation at this point.

Why these nerve impulses, alike in themselves, give rise to such widely different sensations when they arrive at their respective cerebral terminations is a matter beyond the scope of physiological analysis. We have to make use of the fact, to a certain extent, in the investigation of the laws of action of the peripheral receptors. The next point to be noted is that, however these receptors themselves are excited, whether the stimulus is one for which they are specially adapted or not, the sensation evoked is the same. Thus, there are certain spots in the skin which give rise to a sensation of heat, even when excited electrically or mechanically, while there are others which give rise to a sensation of cold when similarly excited. The important point is that specialised receptors are much more sensitive to their appropriate stimulus than to any other. An electrical stimulus strong enough to excite a heat spot excites also a cold spot or a pressure spot, whereas a warm body is able to excite a heat spot when its stimulus is too weak to excite any other kind of receptor. A warm surface thus stimulates only the heat spots, until its temperature is raised sufficiently high to be nocuous and to cause pain. It is possible that the inappropriate stimulus needs to be strong enough to excite the actual nerve fibres themselves, in which case we are clearly dealing with Miiller's law itself.

Weber's Law. — As this law is of general application, it may properly be referred to here. It refers to the increase of the sensation, as related to that of the stimulus, and states that, in order to produce a just detectable difference in sensation, an equal fraction of the stimulus must be added to it, whatever its value. Suppose that we could just detect the difference between 10 g. and 11 g., it would be necessary to add 100 g. to a kilogram before the change was noticed. Thus to increase a weak sensation by a given amount requires a less addition to the stimulus than to increase a strong sensation by the same amount. The law is a particular aspect of a law frequently met with in natural phenomena.

It may be put in another form. To excite a series of sensations differing by equal increments, the stimuli must increase in geometric proportion. If the logarithms of the stimuli are plotted as abscissae, and the sensations as ordinates, a straight line is produced. Victor Henri et Larguier <lcs liuncels (1912) point out that the law applies to vision in the middle of the range of stimuli only. The curve, drawn as above, with logarithms as abscissa;, is, as a whole, of an S-shape. Similar relations between stimulus and effect apply to the electrical changes in the retina, according to the results of De Haas, and also, as regards the middle region, where the curve is practically a straight line, to the action of ultra-violet light on Cyclops, as studied by Mme. Victor Henri et Victor Henri, whose work will be referred to in a future chapter. The conclusion to be drawn is that, in all probability, Weber's law rests on physiological phenomena as its basis.

We pass on to refer, somewhat briefly, to certain facts regarding the different kinds of sense receptors. Owing to its interest and importance and partly, perhaps, on account of the comparative ease with which it can be investigated up to a certain point, this branch of physiology has produced as much work as any other, probably more. Certain individual sense organs, as the eye and the ear, have large textbooks and memoirs devoted to the^n alone, or even to particular aspects of them, as, for example, the refractive properties of the dioptric system of the eye. I must be content, therefore, with referring the reader to some of these memoirs for the greater part of the information available (see the list of literature at the end of this chapter).

It is well known that a variety of sensations are obtained by means of the skin. Heat and cold have been already referred to ; these were shown by Blix (1884) to arise from distinct spots, as also the sense of pressure. Von Frey (1894) showed that there are also distinct pain spots. To the latter investigator we owe most of our knowledge on the question, and his article (1913) may be read with profit. Von Frey's use of delicate hairs, the degree of pressure exerted by each being determined by the weight required to bend it, should be mentioned.

It is impossible to give, at present, an adequate explanation how small differences of heat and cold are magnified sufficiently to excite nerve fibres. Various possibilities might be mentioned, such as a chemical reaction greatly accelerated by heat or some physical mechanism making use of expansion to cause pressure. Pressure stimuli themselves may perhaps be increased by some kind of lever action, as in the case of the long bristles forming the whiskers of the cat, which seem to be sensitive even to air currents, since it is difficult otherwise to suggest an explanation of their guiding power in the dark.

The various modifications of the sense of touch are brought about by combination of movement with contact, by which a series of sensitive points is excited, or the same spot by a series of stimuli occurring at different rates. In this latter connection, the possibility may be referred to that a nerve fibre may have synapses with two neurones and that the refractory period in one synapse may be longer than in the other. . Thus, a slow rate of stimuli may pass both unaltered, while a rapid rate will pass only one unaltered, being reduced to a slow rate in the other one. In this way, there seems to be an indication of the way one nerve fibre might serve to convey impulses giving rise to different sensations. An economy of nerve fibres might possibly be brought about, a point of importance in connection with the very fine gradations in the higher senses, but it is purely hypothetical. There is another point to be remembered here. The roughness of a surface appears to be the same although the finger is moved over it at different rates. This fact indicates that it is not merely the different number of stimuli affecting the nerve ending in a given time that conditions the nature of the sensation, but that this is combined with the sensation of movement given by the muscular sense. So that doubt is cast on any interpretation which assumes that the absolute number of stimuli per second is a controlling factor in different species of sensations.

Protopathic and Epicritic Sensibility. — This is the appropriate place to refer to the experiments of Head, Rivers, and Sherren (1905) on the time of regeneration of various skin sensations. Head caused to be divided the radial nerve (a purely sensory nerve) in his own arm and observations were then made on the returning sensibility. The results led him to regard the sensations derived from the application of stimuli to the hand to be of three different groups : protopathic, epicritic,