Report of tfyc Section op ptjy- 
?apd Pathology. 
RECENT DISCOVERIES IN THE PHYSIOLOGY OF 
GANGLION CELLS. 
By H. Newell Martin, M. A,, M. D., D. Sc., F. R. S., 
Chairman. 
It has been the custom for the chairman of the section 
which I have the honor to represent to-day to search recent 
physiological literature for some topic which may be of 
special interest to medical men. The literature of physiol- 
ogy is now so voluminous, and one has to seek it in so many 
journals, that even the physiologist himself cannot keep 
abreast of it, much less the busy practitioner. On making 
such a search it occurred to me that some work done during 
the last three years on the structure of ganglion cells and the 
changes undergone by ganglion cells when they were irri- 
tated would have interest for you, especially as it seems to 
open up quite new branches of research in the pathology of 
the nervous system. 
Thanks to the work of Heidenhain and Langley, we have 
known for several years that the cells of a gland at work 
differ in their microscopic appearance, and differ in their 
staining qualities, from the cells of a gland at rest; and it 
occurred to Mr. Hodge—then at the Johns Hopkins, now at 
the Clark University—it occurred to him to see if he could 
not discover whether histological changes take place in 
ganglion cells when they are stimulated. 
I may use a moment in recalling to your memory the 
structure of the typical spinal ganglion cell, the cell marked 
Ain the diagram. There you see the capsule, with its many H. NEWELL MARTIN, M. A., M. D., D. SC., ?. R. S. 
nuclei, surrounding the cell, generally supposed not to be 
nervous but of connective tissue nature. Within the cap- 
sule we have the general granular cell substance, containing 
in the typical cell a rounded well defined nucleus, sharply 
marked off from the general protoplasm of the cell and with a 
single nucleolus in it. When prepared as this specimen was, 
by the aid of osmic acid, the nucleus shows a few darkly 
stained points around the nucleolus, but most of it remains 
clear and unstained and is a conspicuous whitish object in 
the general darkly stained mass of the osmic acid specimen. 
It will hardly be necessary for me to go into details as to 
Dr. Hodge’s earlier work, because, Wse most work of the 
kind, one has to begin tentatively and find out the best 
methods and the way to get the best results. In general I 
may say that his hardening was done by alcohol, and his 
subsequent staining either by osmic acid or by what is known 
as the Gaule method, which those of you who are histolo- 
gists will remember. His work does not constitute the first 
set of observations made on histological changes produced 
in ganglion cells by various conditions. Some researches 
had been made on nerve cells at rest compared with gan- 
glion cells in pathological conditions, with the result that 
the most marked changes in the cell were found in the 
nucleus ; and some ten or eleven months after Dr. Hodge 
published his preliminary communication in the American 
Journal of Psychology, there appeared a paper in which ob- 
servations were made by stimulating one sciatic nerve in a frog 
while leaving the other at rest, and subsequently comparing 
sections of the two sides of the spinal cord to see if the cells 
differed in appearance ; it was found that the nuclei of the cells 
on the two sides were a little different in their relation to stain- 
ing fluids. It had also been noticed that in starved animals the 
nuclei of the nerve cells seemed shrunken and the protoplasm 
less dense^morHor/vacuolated than normal; but Dr. Hodge 
was the pioneer in the discovery that stimulation of normal 
ganglion cells caused changes in them, which could be 
recognized with the aid of the microscope. 
His work has been continued at Clark University with 
the greatest care. In order to get comparative results it SECTION ON ANATOMY, PHYSIOLOGY AND PATHOLOGY. 
3 
was necessary to know the strength of the electrical stim- 
ulation, (that he used electrical stimulation I need hardly 
say). That was done by aid of galvanometer and rheochord, 
and every device was used to keep the strength of the stim- 
ulating current uniform. Then apparatus was devised to 
secure that the number of stimulations given in a second to 
the nerve was always the same : so each animal so far as one 
can assume that one young cat is like another young cat 
was brought under practically the same conditions. 
His first idea was to etherize or curarize the animal in 
order to keep it quiet; but observations on animals who had 
been given curare or ether showed that those drugs brought 
about changes in the nerve cells apart from all extrinsic nerve 
stimulation ;so it was necessary to eliminate their use. That 
was done by a method devised by Ludwig some years ago, 
in which a small hole is trephined in the skull of the animal, 
then a thin blunt glass rod introduced and passed through 
the brain until it reaches the crura cerebri. Both crura are 
destroyed by moving the rod to and fro, and thus all motor 
and sensory paths from the cerebral hemispheres to the lower 
parts of the body are cut off. After the operation the animal 
immediately goes into a state of apparently sound quiet sleep, 
and under those conditions it is experimented upon. Dr. 
Hodge used kittens, and each animal was carefully packed in 
cotton batting after destruction of the crura and its tempera- 
ture observed from time to time and kept as constant as pos- 
sible. So far as I can see every precaution to ensure reliable 
results was taken. 
Next, the brachial plexus was exposed on the right side of 
the body and placed between electrodes and, by clockwork 
during the continuance of the excitation, the nerve was 
stimulated for fifteen seconds out of every minute, and rested 
the remaining forty-five ; and so on, minute alter minute ; 
thus in five hours stimulation the nerve would have had on 
the whole an hour and fifteen minutes of stimulation, and 
during the remainder of the time would have been at rest. 
The lower part of the nerves going from the brachial 
plexus to the muscles of the forelimb was not divided, and H. NEWELL MARTIN, M. A., M. D., D. SC., F. R. S. 
4 
the test that the sensory fibres were probably active was that 
the muscles always moved when the stimulus was applied. 
Since the muscles responded to the stimulus, showing the 
motor fibres were irritable, it was assumed that the sensory 
fibres going to the spinal ganglion were also irritable. 
Working in this way Dr. Hodge found on staining the gan- 
glion cells remarkable changes ; those changes are of three 
kinds, and come on in different order. In the first place, the 
nucleus of the stimulated cell loses its well defined contour, and 
takes more of the appearance of the nucleus of the figure' 
marked Bin the diagram. In the second place, the body of the 
cell loses its general dark granular appearance and becomes 
vacuolated, filled apparently with little spaces containing 
liquid, instead of the ordinary granules which normally fill 
the interstices of the meshwork of fibrils which constitute 
the essential part of a ganglion cell. Third, and most re- 
markable, though Dr. Hodge only refers to it and does not 
attempt to explain it, the nuclei of the capsule which sur- 
rounds the ganglion cell and are not part of it at all, undergo 
changes. They shrink and become spherical rather than 
oval. It may be that the waste products secreted by the 
stimulated nerve cell affect these nuclei of its capsule. 
Dr. Hodge takes up next the question whether these 
changes are physiological and not pathological ; whether 
they are due to this gross method of electrical stimulation ; 
which must be more crude than the normal afferent nerve 
impulse : if normal, the changes ought to be progressive with 
increase of the time of stimulation. This he tested by having 
the nuclei measured by persons who did not know what 
had been done to the cells, who dici not know anything 
about the object of the research, but simply sat down to 
measure nuclei in their diameter : the concurrent testimony 
of these observers shows that the diminution of the diameter of 
the nuclei increases as the time of stimulation increases. 
If you stimulate one hour you will get perhaps an average 
diminution in volume of the nuclei as calculated from their 
diameters of about fifteen per cent. If you stimulate two 
hours, the diminution is not much more marked. If you 
stimulate four hours, the average diminution in volume of SECTION ON ANATOMY, PHYSIOLOGY AND PATHOLOGY. 
5 
the nuclei of the stimulated side is thirty-five per cent., and 
after prolonged stimulation of eight hours, sometimes the 
diminution in volume was as much as sixty per cent. 
One point that is important I omitted to mention in its 
proper place. As soon as the stimulation is finished the 
kitten is killed as quickly as possible, the eighth cervical 
ganglion on each side excised and the two put together 
in the same hardening fluid, they are fixed together on the 
same slide, stained in the same vessel, mounted side by 
side in the same paraffine, and cut with the same stroke of 
the knife, so that as far as any action of any reagent on the 
ganglion of the right side which had been and 
on the ganglion of the left side which was left at rest, there is 
no possibility of the reagents producing any of the differ- 
ences observed. 
Next came the thought, if this change in the ganglion 
cells be really a result of their physiological activity, if they 
lose matter and alter their structure during functional activ- 
ity, then they ought to recover with rest, and the recovery 
ought to be proportionate to the time of rest; and in a paper 
which has just appeared in the last number of the Journal of 
Psychology Dr, Hodge discusses that question. 
Taking a number of kittens, from six to eight weeks old, 
they were well fed and then experimented upon ; after 
experiment they were given no food until they were killed. 
Each animal was used for five hours, each minute of each 
hour indicating fifteen seconds of stimulation and forty- 
five seconds of rest. Then one kitten was killed at once, 
another was kept an hour before it was killed, a third two 
hours, and so on. The general result was this : In the 
kitten killed immediately, there was very great histological 
difference between the ganglion of the stimulated and un- 
stimulated side. In the kitten killed an hour later the differ- 
ence was less, the nucleus had begun to enlarge again, and 
did not stain quite so deeply with osmic acid ; and so it went 
on hour after hour, but even at the end of eighteen hours 
the nucleus on the stimulated side was smaller than the 
nucleus on the rested side. At the end of twenty-four 6 
H. NEWELL MARTIN, M. A., M. D., D. SC., F. R. S. 
hours, however, most of the nuclei of the right ganglion 
(the stimulated one), had returned to the histological condition 
of the normal resting ganglion cell. 
I have received within the last few days a note from Dr. 
Hodge, in which he says he is now applying this method to 
the normal alternations of rest and work in animal life. He 
first tried it with kittens and cats, but it is very difficult to 
get animals of that kind to sleep any definite nnmber of 
hours. It occurred to him that birds had more regular 
habits as to sleeping and waking hours than any other animals. 
He tells me, though not ready for detailed publication, thathe 
finds very distinctly in English sparrows the same difference in 
ganglion cells at the end of a day, as compared with the 
ganglion cells of a sparrow killed early in the morning, that 
he finds between the rested and stimulated ganglion cells in 
the kitten. 
It seems to me that this method of research which proves 
that one can discover by histological methods what special 
nerve centre has been active, combined with the recent dis- 
covery of Langley that we can by local application of nicotine 
throw certain ganglia out of functional activity for a time, puts 
us on a whole new course of investigation, or two new courses 
of investigation in regard to the physiology and pathology 
of the nervous system. Ultimately I think these methods 
will come to be used largely in the localization of nerve func- 
tion instead of the more gross surgical methods we have 
now at our disposal. With this future prospect it seemed 
to me that it might interest you to hear about them : and that 
is my excuse for intruding upon your time to-day.