Principles of General Physiology

The heart muscle shows particularly well certain characteristics which are known to apply to all muscle, and others which probably apply. These phenomena are : "all or nothing" in respect of strength of stimulus; "staircase," by which, after a rest, successive contractions increase in height for a time, and probably due to increase of hydrogen ions to the optimum point ; " refractory period," as already described for nerve ; in certain conditions, summation of contraction ; and great sensibility to certain ions, especially those of hydrogen.

There is no transmission from fibre to fibre in skeletal muscle. It does, however, take place in smooth muscle. It is not certain whether, in all cases, the spread of excitation in all directions is conveyed by an intramuscular nerve network, although it appears to be done by that of the Medusa. In warm-blooded animals, heat produced in muscular contraction is utilised for the purpose of keeping up the temperature. The production of heat is measured experimentally by specially constructed calorimeters, which also allow the respiratory metabolism to be determined simultaneously.

In adult animals at rest the production of heat is proportional to the external surface, that is, to the loss. In work, since the muscles are producing heat in excess, it approximates more to proportionality to weight. The temperature is regulated either by change of production, that is, by greater activity or rest, or by change of loss, as by cutaneous vascular changes and by evaporation of water in sweat and expired air. The co-ordinating centre of these factors of regulation is in the corpus striatum, and is so arranged that it is sensitive to changes of temperature in the blood. When warmed, this centre responds by causing muscular relaxation and dilatation of skin vessels, thus producing a fall in body temperature. Conversely, when cooled, it causes a rise in body temperature by exciting muscles to shivering and by vascular constriction in the skin. It is probably also sensitive to afferent impulses from heat and cold receptors in the skin.

A certain degree of control of heat production appears to be the earliest form of regulation, and is present in a rudimentary form even in cold-blooded animals. As far up as Echidna, there is no other mechanism. The possible modes of origin of rhythmical contraction are discussed in the text. In plants, movements are produced by changes of turgor, due to changes of permeability, on excitation by various means. These changes of form are, in many cases, afterwards fixed by differences in rate of growth.

A short account is given in the text of the graphic method, as used in physiological work, together with some practical details. THE necessity of means of bringing into relation with each other the different parts of an organism, as it grows in size and complexity, has been already alluded to (page 378). Moreover, the same muscles may require to be put into action, say for flight, when an animal either sees an enemy or is touched by one, or for the obtaining of food. If there were nerve channels directly connecting every sense organ with every muscular group, the multiplicity of communications would be most wasteful, besides inefficient for its purpose. The comparison of the central nervous system to a telephone exchange is often made, and is quite appropriate. Any subscriber can be put into communication with any other. Similarly, in the animal, impulses arriving from a particular source may be, according to circumstances, connected up, as it were, to different muscular mechanisms. It will be seen that, since the arrangements of a telephone exchange are mainly a matter of wiring, so, in great part, the study of nerve centres consists of the anatomy of tracts of nerve fibres ; a study which tells us of the possible ways of communication between the centres controlling various parts. This aspect of the subject can best be studied in textbooks devoted to it, and will only be treated incidentally in this book. An account, in some detail, will be found in Starling's book (1912, pp. 324-632).

There is another aspect, which is of a more general nature, and consists in the investigation of the means by which the functional use of the paths provided is arranged for. The co-ordination of the activities of various parts of the organism, or integration, as the essential function of the central nervous system, is especially insisted on by Sherrington (1906). When we consider that in the organism, just as in the community, progress depends on the most effective working together of the component units for the common good, we see how, as Gaskell has shown (1908), the nervous system has been the dominant factor in evolution. Other systems have been modified and changed in function in order to give opportunity for the growth of this pre-eminently important one. As Gaskell puts it (p. 19), " The law of progress is this — The race is not to the swift, nor to the strong, but to the wise."

Different views have been put forward with regard to the way in which nerve centres first made their appearance. A brief account will be found in the paper by G. H. Parker (1911). The most satisfactory hypothesis seems to be that of this investigator, who finds that sponges, although no nervous structures are to be found in them, and although they exhibit none of the characteristic rapid reactions of animals with even the most primitive nervous system, do nevertheless show contractile response to stimuli. The opening and closing of oscula takes place in response to movements of the sea water and is brought about by contractile tissue, similar in its appearance and slowness of response to smooth muscle in the higher animals (see Parker's paper, 1910).

Muscular tissue makes its appearance, then, before nervous tissue. Even if we regard the sponges as arising from protozoa by a branch which is separate from that taken by the Coelenterates, it must be admitted that their organisation is a more primitive one than that of the latter and nearer to the ancestral forms. Parker's theory regards the muscle cell, or " effector," as developed from amoeboid epithelium and as being gradually displaced to form a layer underneath the external epithelium. " Next in sequence would appear the receptor or sense organ which, derived from the cells in the neighbourhood of a developed effector (see Fig. 141), would serve as a more efficient means (D) of calling this organ into action than direct stimulation. This stage is represented by many Ccelenterates ; and their quick responses, as compared with those of sponges, are dependent, I believe, upon this advance in organisation. Finally, in forms somewhat more advanced than the Ccelenterates, central nervous organs or adjusters would begin to differentiate in the region between the receptors and effectors ; and these would develop in the higher animals first, as organs of transmission whereby the whole musculature of a given form could be brought into co-ordinated action from a single point on its surface and, secondly, as the storehouse for the nervous experience of the individual and the seat of those remarkable activities that we recognise in the conscious states of the higher animals. Thus nerve and muscle did not develop independently, as claimed by Glaus and Chun, or simultaneously, as maintained by Kleinenberg and the Hertwigs, but muscle appeared first as independent effectors and nerve developed secondarily in conjunction with such muscles, first as a means of quickly setting them in action and, secondly, as a seat of intelligence" (Parker, 1911, pp. 224-225). The same author further points out (1909, p. 58) that a receptor or sense organ alone would be of no service to an organism, neither would nerves nor nerve centres alone, whereas a muscle cell, or effector, is of use, if it can be stimulated directly.

It is thus not improbable that there should be primitive multicellular animals possessing effectors only and neither cells sufficiently differentiated to be called receptors nor other nervous mechanisms. The next step in evolution after that of the sponges is the receptor-effector system, as seen in its simplest form in the sea anemones, and, with more complication, in the jelly-fish. The outer surface of a sea anemone is found to be diversely sensitive for different kinds of stimuli and, moreover, the response to stimulation of a tentacle may be a movement in a distant part of the organism, without any movement of intermediate regions, so that something in the nature of nervous transmission is present. On histological examination, the skin of these animals is found to consist of three layers. An outer one contains epithelium cells modified to serve as sense receptors, having bristles on the outer ends. Their inner ends are prolonged into finely branched processes, clearly of nervous nature, which intermingle with those of other cells to form the second nervous layer. This layer also contains cells with branched processes, which intermingle with the rest, in fact, ganglion cells. It appears that this layer constitutes a true nervous network, continuous over the whole body, and that no centralisation of the adjuster mechanism has yet taken place. The third layer consists of muscle cells in contact with the nerve network. Experiments of various kinds show that the reactions of one part of the body do not serve as experience for another, that is, it shows no evidence of what we should call a central nervous system (von TJexkiill, 1909, p. 73). Its neuro-muscular system consists of receptors and effectors, united by a nerve network, which is composed of the processes of receptor cells and of ganglion cells contained in the network.

The jelly-fish, owing to their locomotion, lead a life subject to greater variety of experiences, and we find specialised forms of receptor organs, which are much more sensitive than those of the sea anemone. The muscular band is under the control of a nerve network, which receives numerous fibres from the receptor organs. This network conveys the excitatory process from one part to another, since contraction can pass from one group of muscle fibres to another over a gap containing network but no muscle fibres. It also conveys excitation in all directions ; if all the sense organs but one are removed, the rhythmic impulses to swimming movements are started by this one and radiate from it in all directions.

Proceeding upwards, we find in the earthworm a centralised nervous system, a diagram of which, taken from the description and figures of Retzius (1892), is given in Fig. 142. In this animal we have a cerebral ganglion, or brain, in the anterior end, and a segmented nerve cord passing along the ventral middle line and extending to the posterior end. The integument contains many sense cells, each giving rise to a single nerve fibre, which enters a ganglion of the ventral nerve chain and divides therein into numerous branches, forming the so-called neuropile. Whether this neuropile is actually a network, that is, whether there is actual physical continuity between the branches of different cells, is difficult to make out. But it seems that we have here a definite system of " neurones," which play so large a part in the higher nervous systems.

The name "neurone" was given by Waldeyer (1891, p. 1352) to the elementary unit of which the higher nervous systems are built. A motor neurone consists of a cell body, with a nucleus, a nerve fibre conveying excitation from the cell body outwards, and which may be long or short, together with a number of branched processes or " dendrites," receiving impulses from outside the cell. The nerve fibre process usually ends in a branched form either on the cell of an effector organ of some kind, muscle, gland cell, etc., or on another neurone. In the sensory neurone, the long fibre usually receives the impression from the exterior and conveys it to other neurones by the dendrites. The peculiarity of a neurone, as compared with other cells, is the possession, in the larger animals, of

great length ; it may have its cell body with nucleus in the brain at the anterior end of an animal of several feet in length, while the termination of its outgoing process, the axis cylinder process or axone, may be on a nerve cell at the distant end of the spinal cord. There is no actual continuity of protoplasm where neurone joins neurone, merely contact, thus differing from a nerve network, and giving rise to very important properties of the higher nervous systems. We shall return to the elementary properties of the neurone presently.

In the earthworm, then, we have a primary sensory neurone, with its cell body in the skin, and its nerve process ending in ramifications in the neuropile of the segmental ganglia. In these ganglia, we find also large nerve cells, whose thick axones pass out as motor fibres to the muscles of the body wall. These motor neurones also are possessed of dendrites, which contribute to the formation of the neuropile and form connections, either of direct continuity or merely of contact, with the endings of the sensory neurones. This is the simplest possible reflex arc, sensory impressions giving rise to a motor response.

In the central nervous system of the earthworm, we find also association neurones ; these have processes serving to connect neurones within one ganglion, or from one ganglion to another, but rarely extend over more than two segments. These neurones do not pass out of the central nervous system, and it may be noted here that the complexity of this system, with rise in the scale of evolution, depends on the number and length of these association neurones ; so that we reach finally the cerebral cortex of the higher apes and man, which consists entirely of this kind of neurones, having no direct connection with the exterior. It is not difficult to understand why specially sensitive and elaborate receptor organs should

C, Partially differentiated nerve cell in proximity to the fully differentiated muscle cell. be developed at that end of an animal which is most exposed to the complexity of outer influences. The cerebral ganglia have, no doubt, been formed in relation to these manifold sensory impressions, and long association neurones have been developed in order that slight influences, able to affect the delicate receptors in the head but not the less sensitive ones elsewhere, may affect distant parts of the organism.

As we proceed upwards, we rapidly gain complexity and efficiency by the development of these long association neurones, which are indeed the only fundamental difference between the higher and lower invertebrates. In the vertebrates, the primary motor neurones have their cell bodies in the central mass, like the invertebrates, but the primary sensory neurones, instead of having their cell bodies in or near the surface, have undergone a change in situation, so that the cell body is placed, as it were, on a side branch of the nerve fibre close to

FIG. 143. DIAGRAMS OF THE EVOLUTION OF THE CENTRAL NERVOUS SYSTEM. S, Sensory neurone. A, Association neurone. M, Motor neurone. e, Epithelial cell. m, Muscle cell. The dotted lines indicate the boundaries of the nerve centres. 5. Exceptional, simple, reflex arc in vertebrates. Possibly exiting in the case of the knee jerk. 0. Usual type in vertebrates. The cell bodies of the sensory neurones are in the dorsal root ganglia, instead of in the receptor organs, except in the olfactory organ. 7. Addition of higher centres, consisting only of association neurones, some of which are inhibitory. They

form, <w it were, longer and longer parallel or alternative loops between the receptor and effector the central nervous system, and thus the ganglia of the dorsal roots are formed. The olfactory nerve alone retains its primitive condition. Whether there is any actual continuity, of the nature of that presumed to exist in a nerve network, in the case of the neurones forming the nerve centres of the vertebrate, has been somewhat disputed. The evidence is of a very doubtful character, and the relation by contact with the interposition of a " synaptic membrane," as it is called by Sherrington (1906, pp. 15-17), becomes marked and predominant.

When the axone is cut off from its cell body, it undergoes a process of degeneration, as a part of any cell, except that containing the nucleus, does. Owing to the large number of long neurones in the vertebrate, section of their nerve centres results in extensive degeneration, contrary to what obtains in animals like worms. The degenerations following known, localised injuries form an important method of investigating the manner of connection of one part of the central nervous system with another.

A fact to which Parker calls attention (1909, pp. 338-345) is the origin of effectors, other than muscles, such as chromatophores, glands, phosphorescent organs, etc., which, like that of muscle itself, appears to be independent of that of the central nervous system and to be continued throughout the course of evolution. These effectors become appropriated by the nervous system, as it grows in its power of control. Many of the facts referred to above may be made clearer by reference to the diagrams of Fig. 143.

The most striking morphological fact with regard to the vertebrate nervous system, as compared with the invertebrate, is that, although the cerebral mass or brain in both cases lies in front of and above the alimentary canal, the continuation along the body — spinal cord in the vertebrate, ganglionic chain, or similar set of ganglia, in the invertebrate — has a different relationship to the alimentary canal, being dorsal to it in the vertebrate, ventral in the invertebrate. Now Gaskell (1908) has brought forward a theory, supported by a large body of evidence and entirely in agreement with the pre-eminence of the nervous system, according to which the vertebrate nervous system is in direct continuity of descent with that of the invertebrate. The ventral ganglion masses grow up, as they increase, to surround the primitive alimentary canal, which finally becomes the central canal of the spinal cord in connection with the ventricles of the brain. This necessitates, of course, the formation of a new alimentary canal, which takes place by enclosure of a space by downgrowth of the body walls ventrally. There is really no more difficulty in this, as Gaskell points out (1908, p. 58), than in the production of a new respiratory system in the passage from fish to land amphibians and less difficulty than in supposing that a new nervous system was developed. The way in which this view accounts for many curious features in the erabryological development of the vertebrate nervous system can only be appreciated by consultation of Gaskell's book.

We may next proceed to consider, briefly, some facts as to the general structure and function of the elementary constituents which make up the nervous system, omitting, for the present, the question of the nerve network. One of the most striking characters of the neurones, at all events in the higher vertebrates, is that, contrary to the cells of other organs, the whole of those which the adult animal is to possess are present at birth, gradually taking on functional activity. There is no evidence of any regeneration after destruction or death of any individual neurone. Although there are great varieties in detail, especially in size and shape, in the neurones of different function, they all consist of a nucleus surrounded by cytoplasm, and have an unbranched process which may, however, divide peripherally — the axone ; they have also branching processes, the dendrites, which also communicate with those of other neurones, as mentioned above.

Certain observers, by examination of nerve cells fixed and stained in various ways, have shown that, under these conditions, there are two obvious structural elements in the cytoplasm : (1) Large granules or masses which stain deeply with "basic" dyes, and are called, from their discoverer, "Nissl Bodies," and (2) an appearance of fine fibrils passing through the cell substance from one process to another, "neuro-fibrils." Now Mott (1912) and Marinesco (1912) have made very careful examinations of living nerve cells, partly by the aid of the ultra-

a, Normal cell, from dog three days old. Fine colloidal particles in cytoplasm, showing Brown jan movement. Nucleus appears nearly empty. No indication of Nissl bodies, nor of neuro-fibrils. No amoeboid movement of the cell as a whole was noticed. b, Similar cell from new-born dog. More highly magnified. Collection of particles around nucleus. c, From ganglion in lumbar region of new-born dog. Large, brilliant granules are seen where the axone leaves. **, Five cells from small dog. They showed spontaneous changes under observation. The brighter

areas, due to larger particles, changed their positions in the cells. e, Two cells, which had been treated with sodium iodide for eight hours. Appearance of larger aggregates of particles, surrounded by smaller ones still showing Brownian movement. microscopic method of brilliant dark-ground illumination (see page 82), and agree in the statement that neither Nissl bodies nor neuro-fibrils are present in the living state ; a result which might be suspected from the work of Hardy described in Chapter I. of this book (see Fig. 144). The considerations of that chapter as to cell protoplasm in general apply to that of the neurone. It is seen to be full of fine granules, behaves as a viscous fluid, and, to reagents, responds as an electronegative colloid. Without denying the value of observations on fixed cells, Mott

thinks that the conceptions of neuro-fibrils and Nissl substance are apt to lead astray in the interpretation of phenomena taking place during life. His observations were made on ganglion cells mounted in serum or cerebrospinal fluid of the animal whose cells were under observation, and they were kept at body temperature. The granules are extremely minute, not more than 1 p. in diameter, and they appear themselves to consist of a colloidal solution surrounded by a lipoid envelope. This envelope stains deeply with methylene blue.

The observations of Ross Harrison on the outgrowth of nerve fibres have already been mentioned (page 22). They suggest strongly an amoeboid movement of the processes of the nerve cell, at all events in the embryonic state, and show that the nerve fibres grow out from cells in the central nervous mass, thus placing the neurone doctrine beyond question (see Fig. 20). If this amoeboid nature of the branches of the cells continues in the adult, the possibility is present of influence by changes of surface tension, due to excitation processes in the cell, and an effect on the degree of contact with other neurones.

Contrary to the nerve fibre itself, the cell body of the neurone is very sensitive to deprivation of oxygen, both cytoplasm and nucleus becoming swollen. Similar changes occur when the axone is injured, and the power of recovery depends on the degree of the injury. If recovery takes place, the axone grows out again to the periphery. From the effect of raised temperature, Mott concludes that there are at least two colloidal substances in the living cell, fluid granules with delicate membranes and a viscid homogeneous semi-fluid substance forming the external phase. The membranes on the surface of the internal phase are, doubtless, produced by adsorption. Rise of temperature causes the granules to blend with the external phase.

The fact that each lateral half of the electrical organ of Malapterurus is innervated by one single large efferent neurone enabled Gotch and Burch (1896) to investigate certain elementary properties of the mode of discharge of the nerve cell. Although caution must be exercised in extending these results to all efferent neurones, they give valuable indications of the phenomena possible. The response to a peripheral stimulus is usually multiple, that is, a rhythmical series of discharges. In fatigue, the number of discharges per second is decreased before the intensity of each individual discharge falls. The time taken by an impulse to pass from the afferent to the efferent side of a cell is from O008 to O'Ol second and is increased by fatigue.