But the latter is always present, and is indeed the chief functional constituent of the nerve-fibre. The several parts of which the nerve-fibre is composed may now be described in detail.

Axis-cylinder.-The essential part of every nerve-fibre is a pale and somewhat indistinct strand, which runs in the axis of the fibre and is termed the axis-band, axial fibre, or more commonly the axis-cylinder (fig. 355, 3; and 356, c). This essential part is usually enclosed, as just mentioned, in one or more sheaths, but these are not always present, especially at the origin and termination of a nervefibre; and even in the course of the fibre they may be interrupted at intervals. The axis-cylinder, on the other hand, undergoes no interruption along the whole course of the nerve, from the nerve-centre to the peripheral distribution. It appears further to be clearly established that the axial fibre of a nerve is in every case a direct prolongation of a branch of a nerve-cell. It is therefore to be looked upon in the light of a far-extending cell-process; and the study of the development of the nerve-fibre affords a direct confirmation of this view of its nature.

In the fresh state, and under high powers of the microscope, the axis-cylinder presents an appearance of longitudinal striation, indicating a fibrillar structure (fig. 35,7); and at the termination of the nerves it may often be seen to separate into a

a

B

Fig. 358. NERVE-FIBRES STAINED WITH NITRATE OF SILVER TO SHOW
FROMMANN'S MARKINGS IN THE AXIS-CYLINDER. (Ranvier.)

A, fibre showing a node, a, with the constricting ring. The axiscylinder has become shifted, and the part which was opposite the node and which is stained by the silver, is now below it; r, conical enlargement of the axis-cylinder.

B, Isolated axis-cylinder.

number of exquisitely fine filaments or fibrils. These, the primitive fibrille of Max Schultze, are embedded in a homogeneous or finely-granular material, and may with some reason be regarded as constituting the essential or conducting part of the axis-cylinder, and therefore of the nerve; at least, it frequently happens that they form the only visible portion of the nerve-fibre that is prolonged to the ultimate termination. The fibrils often exhibit minute varicosities which are highly characteristic in appearance. They have a remarkable affinity for gold salts, and when placed first in solutions of these and afterwards in reducing agents (or merely exposed to the light in water), the metal becomes deposited in the nerve-fibrils, giving them a dark violet, almost black, appearance (see fig. 407, p. 346). They also become deeply stained by methyl blue, especially when it is injected into the vascular system of the living animal (Ehrlich). These methods are employed to trace the mode of ending of the fibrils.

The axis-cylinder is, by some authors, stated to be invested with a very delicate structureless sheath. This sheath, which was first described by Mauthner, may possibly be a protoplasmic inner layer of the medullary sheath; but it is somewhat doubtful whether the appearance is not due to a layer of fluid which has become expressed by a shrinking of the axis-cylinder and coagulated under the influence of the reagents employed.

It was shown by Frommann that after treatment with nitrate of silver and subsequent exposure to the light the axis-cylinder becomes stained in such a manner as to exhibit a distinct cross-striated aspect (fig. 358), but it is not known whether this depends upon any structural feature of the fibre or not. In addition to this cross-striated appearance, which may be seen in any part of the axis-cylinders, they exhibit a peculiar biconical enlargement at each node

of Ranvier when thus treated, the enlargement corresponding in situation to the annular constricting band of the node (Ranvier).

It is not always easy to distinguish the axis-cylinder in the medullated fibres when they are examined in the fresh condition, but it can generally be made manifest by staining the nerve with carmine or hæmatoxylin. In a transverse section of a nerve thus stained the axiscylinders appear in the form of round or oval areas occupying the centre of the fibres (fig. 362), but they are often much shrunken. The fibrils of the axis-cylinder have a tubular aspect in a well prepared section, which is distinctly visible in photographs under a high power.

Fig. 359.-PORTIONS OF TWO NERVE-FIBRES STAINED WITH OSMIC ACID (FROM

A YOUNG RABBIT). 425 DIAMETERS (E. A. S.).

R, R. Nodes of Ranvier, with axis-cylinder passing through. a, Primitive sheath of the nerve; c, opposite the middle of the segment indicates the nucleus and protoplasm lying between the primitive sheath and the medullary sheath. In a the nodes are wider, and the intersegmental substance more apparent than in B. (From a drawing by Mr. J. E. Neale.)

Medullary Sheath.-The myelin or substance of the medullary sheath (which was termed the white substance by Schwann on account of its presence being the chief cause of the whiteness of the nerves), undergoes peculiar changes on exposure of the nerve to the action of water and other fluids, so that the outline of the fibre is often rendered uneven; round and irregular spots appear at various points, the medullary sheath acquiring eventually a confusedly curdled aspect.

The thickness of this sheath varies within wide limits, and indeed this is the chief cause of the variation in size of the medullated nerve-fibres, although the axis-cylinder may also vary in diameter to a considerable extent. In some fibres, the medullary substance forms an exceedingly thin layer, so as to be scarcely distinguishable except by the darker outline which it imparts to the fibre, or it may only occur in parts, these alternating irregularly with other parts in which there is a complete absence of white substance. Such fibres, which are common in some parts of the sympathetic system (fig. 365, m, m), may be regarded as transitional between the white and the grey fibres.

Nodes and internodes of Ranvier.-It was shown by Ranvier, that there constantly occur in the peripheral medullated nerve-fibres, breaks in the continuity of the white substance, which succeed one another at regular intervals along the course of the nerves, and give the fibres the appearance of being constricted at these places. These constrictions or nodes of Ranvier, as they may conveniently be termed, divide the fibre into a series of internodes of nearly equal length. The segmentation is readily made apparent by the action of a solution of osmic acid, which leaves the nodes (fig. 359, R, R; fig. 360) almost colourless, while the medullary sheath, or white substance of Schwann, becomes stained of an inky black colour.

The white substance of the medullary sheath is often found to have shrunk somewhat in the neighbourhood of a node (fig. 356, A), and it can then be seen that there is present, in addition to it, a clear or finely granular stroma, which has become evident in consequence of retraction of the fatty substance which normally pervaded it.

The outer or membranous sheath of the fibre (neurolemma) appears to be continued over the nodes, for when a medullated fibre is examined in water and the substance

of the medullary sheath exudes from the cut ends of the nerve-fibres, it is found that the place of that which thus escapes is taken by the white substance from the next internode; and this substance may be seen to flow past the constrictions of Ranvier without escaping at those points. Within the primitive sheath the internodes are united by an annular disc-the "constricting band" of Ranvier-the nature of which is unknown, although like intercellular substance elsewhere, it becomes stained by nitrate of silver. The last-named reagent stains also the axiscylinder in the neighbourhood of the node in the manner indicated by Frommann (see page 310), so that the fibres after this treatment appear marked with little crosses (fig. 381); the transverse limb of the cross being due to the ring of intersegmental substance, the longitudinal to the axis-cylinder. Many other fluids stain the axis-cylinder at the nodes only, being prevented from reaching it elsewhere owing to the presence of the fatty matter in the surrounding medullary sheath.

The division of nerve-fibres always occurs at the site of a node of Ranvier (see fig. 388, p. 333).

Engelmann argues in favour of a discontinuity of the axis-cylinder (as well as of the medullary sheath) at the nodes of Ranvier, basing his argument partly on the fact that the

A

B

degeneration which results above the section when a nerve-fibre is cut, stops at the first node of Ranvier, partly on appearances obtained after a certain method of treatment with nitrate of silver, a dark deposit characteristic of inter-cellular substance traversing, according to the account given by him, the thickness of the axis-cylinder at the nodes. He also points out that the axis-cylinders very readily become broken across at the nodes. This view has been in a measure confirmed by the researches of Gedoelst, who has shown that there is a tendency at the nodes of Ranvier for the fibrils of the axis-cylinder to develop minute swellings or nodosities which closely resemble those which are formed upon the achromatic fibres which unite the two daughter-nuclei of a dividing cell in most vegetable and some animal tissues (Zell-platte of Strasburger) and which indicate the plane of separation between the two daughter-cells and of formation of the cellulose or other membrane. Such a structure is shown in the representations of a dividing ovum given by

Strasburger (see fig. 218, p. 188), and is superficially very similar to that figured by Gedoelst upon the axis-cylinder at the nodes (fig. 360). But the identity of the two structures in spite of this superficial resemblance must not be taken as proved. The axis-cylinder is not an out-growth from a nucleus, nor can its segments be taken to represent nuclei. Neither do its fibrils resemble in chemical characters so far as is known the achromatic fibrils of a cell-nucleus. But in spite of these differences the correspondence between an inter-node of a nerve and an elongated cell is so direct and obvious that a view which permits of the presence of the nodes of Ranvier being explained as indicating a tendency of the fibre to become divided across into cell-segments cannot be altogether disregarded. Ranvier, Boveri, and others, have looked upon the medullary and primitive sheaths only as being thus segmented up into cells, which they regard as wrapped around the axis-cylinder. But when first developed the medullary sheath is a continuous and unsegmented layer, and appears to be laid down upon the surface of the pale fibre which is becoming medullated, by the superficial protoplasm of that fibre itself (see Development of nerves).

The internodes or nerve-segments vary in length in different nerves; in larger nerve-fibres they may perhaps, speaking roughly, average about 1 mm. In the nerves of young animals they are often much shorter than this, so that the growth

of nerves in length with the growth of the limbs and other parts of the body is in part due to interstitial elongation of the segments.

In the middle of each internode an oval nucleus lies embedded in the medullary

Fig. 361.-MEDULLATED NERVE-FIBRE TREATED WITH OSMIC ACID (Key and Retzius).

A node of Ranvier (E) and a nucleus (K) is represented. The medullary sheath appears broken up into a number of segments with conical or funnel-shaped ends fitting into one another.

sheath (figs. 356, B, 359, c, 361, K); these nuclei will be described with the primitive sheath.

Medullary segments.-Other breaks of continuity are seen in the medullary sheath (figs. 353, 361) which are of an entirely different nature from the nodes of Ranvier; indeed it is somewhat uncertain how far they correspond to a pre-existent structure in the fibre. In consequence of their presence the medullary sheath appears as if made up of a number of small cylindrical segments with either conical or funnel-shaped ends which fit in with one another in the alternate segments. The segments in question have been frequently described as integral constituents of the medullary sheath (Schmidt, Lantermann and others). It is easy to convince oneself of the reality of the appearances here mentioned, but it is far less easy to be certain that they are not artificial productions. Against the view of their existence in the natural condition it is to be noted that they are extremely variable in number and in size in a given length, even of the same nerve-fibre, that they appear to become increased in number if the nerve-fibre have been subjected to much manipulation, that they have no constant relation, so far as can be made out, to the other parts of the medullated fibre, and that, according to the testimony of several careful observers, they are not to be seen in the nerve-fibres of the living animal, unless these have been subjected to an abnormal amount of traction or other mechanical injury. This last assertion is denied, however, by others, who maintain the pre-existence of the medullary segments, and describe them and the oblique clefts which separate them as definite parts of the sheath. Ranvier on the other hand, who first described the original protoplasmic condition of the medullary sheath, considers that the protoplasm has disappeared and become replaced by the pseudo-fatty substances (lecithin, neurin, &c.), except next to the primitive sheath or neurolemma, and next to the axis-cylinder, where fine layers still remain, and he regards these as being connected with one another by protoplasmic septa, which lie in the intervals between the conico-cylindrical segments of the medullary sheath. In short he regards each segment of the medullary sheath as representing an elongated cell occupied mainly by this fatty material and wrapped round the axis-cylinder.

Careful examination of the fibres in the fresh condition reveals fine obliquely disposed lamellæ, which in optical section have the appearance of fibres, bridging across the clefts between the segments (fig. 353). In nervefibres which have been treated by a mixture of bichromate of potash and osmic acid, and afterwards by nitrate of silver, the situation of each cleft

K

is occupied by what looks like a thread of darkly stained substance passing spirally around the fibre (Rezzonico, Golgi). The meaning of these appearances is by no means clear.

Rod-like and reticular structures in the medullary sheath.—It was

shown by McCarthy that after a nerve has been hardened with chromate of ammonium (picric acid is still better adapted for the purpose) the medullary sheath appears pervaded with minute rod-like structures which pass radially between the axis-cylinder and the primitive sheath in such a manner as to give the cross-section

1000

Fig. 362.-SECTION ACROSS PART OF A NERVE-TRUNK, SHOWING
THE SECTIONS OF THE NERVE-FIBRES (E. A. S.).
(From a photograph.)

The nerve was hardened in picric acid and stained with
picrocarmine. The radial striation of the medullary sheath is
very apparent. In one fibre the axis-cylinder is shrunken and
The fibrils of the axis-
the medullary striations are broken.
cylinder are clear in section and suggest a tubular structure.

of a nerve-fibre the appearance of a wheel. The rods stain with carmine and hematoxylin, which do not colour the fatty substance of the medullary sheath. In nerves stained with osmic acid (in

which these structures were first detected by Lantermann) they are far less easily seen, in consequence of the dark colouration of the fatty substance in which they are embedded. The apparent rods are not distinct from one another, but are united, for it is not possible to isolate them as separate elements.

If a nerve is first placedin strong alcohol and then subjected to the action of staining fluids, it will be found that the rod-like structures are not visible as such, but

A

B

RETICULAR APPEAR

Fig. 363.-NERVE-FIBRES SHOWING
ANCES IN THE MEDULLARY SHEATH (Gedoelst).
A. A nerve-fibre from the toad, showing different
appearances of the network at different parts of its course.
B. A nerve-fibre from the guinea-pig, showing a much
coarser network. n, nucleus of fibre.

the medullary sheath appears pervaded instead by a finely reticular structure, which like the rods, becomes readily stained by most dyes. The network thus obtained is considered by Kühne and Ewald, who first drew attention to it, to be chemically of a horny nature, on account of the resistance it offers to reagents, and especially to digestive ferments, and they have accordingly designated it the horny reticulum or neurokeratin network. They further describe it as continuous with two delicate membranes of a similar nature, one immediately investing the axis-cylinder and The the other lining the primitive sheath. pre-existence of a neurokeratin network is, however, at least questionable. Of the presence both in the nerves and in the white matter of the nerve-centres of the material known as neurokeratin there can be no doubt; it appears probable, however, that its reticular arrangement is a product of the reagent (alcohol) employed to demonstrate it. This at least has been the opinion of most authors who have investigated the subject (Hesse, Pertik, Waldstein and Weber), whereas others, whilst admitting its variability, consider its pre-existence beyond doubt. Gedoelst, who maintains this view of the neurokeratin network, regards it as the reticulum of the original protoplasmic cell from which the medullary sheath of the nerve-segment has been formed. It must be admitted, however, that its