... (T)he same cause, such as electricity, can simultaneously affect all sensory organs, since they are all sensitive to it; and yet, every sensory nerve reacts to it differently; one nerve perceives it as light, another hears its sound, another one smells it; another tastes the electricity, and another one feels it as pain and shock. One nerve perceives a luminous picture through mechanical irritation, another one hears it as buzzing, another one senses it as pain. . . He who feels compelled to consider the consequences of these facts cannot but realize that the specific sensibility of nerves for certain impressions is not enough, since all nerves are sensitive to the same cause but react to the same cause in different ways. . . (S)ensation is not the conduction of a quality or state of external bodies to consciousness, but the conduction of a quality or state of our nerves to consciousness, excited by an external cause.
Law of Specific Nerve Energies.

An immune system of enormous complexity is present in all vertebrate animals. When we place a population of lymphocytes from such an animal in appropriate tissue culture fluid, and when we add an antigen, the lymphocytes will produce specific antibody molecules, in the absense of any nerve cells. I find it astonishing that the immune system embodies a degree of complexity which suggests some more or less superficial though striking analogies with human language, and that this cognitive system has evolved and functions without assistance of the brain.

And if incision of the temple is made on the left, spasm seizes the parts on the right, while if the incision is on the right, spasm seizes the parts on the left.

Each nerve cell receives connections from other nerve cells at six sites called synapses. But here is an astonishing fact—there are about one million billion connections in the cortical sheet. If you were to count them, one connection (or synapse) per second, you would finish counting some thirty-two million years after you began. Another way of getting a feeling for the numbers of connections in this extraordinary structure is to consider that a large match-head's worth of your brain contains about a billion connections. Notice that I only mention counting connections. If we consider how connections might be variously combined, the number would be hyperastronomical—on the order of ten followed by millions of zeros. (There are about ten followed by eighty zero's worth of positively charged particles in the whole known universe!)

For, every time a certain portion is destroyed, be it of the brain or of the spinal cord, a function is compelled to cease suddenly, and before the time known beforehand when it would stop naturally, it is certain that this function depends upon the area destroyed. It is in this way that I have recognized that the prime motive power of respiration has its seat in that part of the medulla oblongata that gives rise to the nerves of the eighth pair [vagi]; and it is by this method that up to a certain point it will be possible to discover the use of certain parts of the brain.

God may forgive your sins, but your nervous system won't.

Hitherto the conception of chemical transmission at nerve endings and neuronal synapses, originating in Loewi's discovery, and with the extension that the work of my colleagues has been able to give to it, can claim one practical result, in the specific, though alas only short, alleviation of the condition of myasthenia gravis, by eserine and its synthetic analogues.

I call that part of the human body irritable, which becomes shorter upon being touched; very irritable if it contracts upon a slight touch, and the contrary if by a violent touch it contracts but little. I call that a sensible part of the human body, which upon being touched transmits the impression of it to the soul; and in brutes, in whom the existence of a soul is not so clear, I call those parts sensible, the Irritation of which occasions evident signs of pain and disquiet in the animal. On the contrary, I call that insensible, which being burnt, tore, pricked, or cut till it is quite destroyed, occasions no sign of pain nor convulsion, nor any sort of change in the situation of the body.

I defend the following postulate as an indisputable principle: that each nerve fibre originates as a process from a single cell. This is its genetic, nutritive, and functional center; all other connections of the fibre are either indirect or secondary.

I have found that a measurable period of time elapses before the stimulus applied to the iliac plexus of the frog is transmitted to the insertion of the crural nerve into the gastrocnemius muscle by a brief electric current. In large frogs, in which the nerves were from 50-60 mm. in length, and which were preserved at a temperature of 2-6° C, although the temperature of the observation chanber was between 11° and 150° C, the elapsed time was 0.0014 to 0.0020 of a second.

I have never had reason, up to now, to give up the concept which I have always stressed, that nerve cells, instead of working individually, act together, so that we must think that several groups of elements exercise a cumulative effect on the peripheral organs through whole bundles of fibres. It is understood that this concept implies another regarding the opposite action of sensory functions. However opposed it may seem to the popular tendency to individualize the elements, I cannot abandon the idea of a unitary action of the nervous system, without bothering if, by that, I approach old conceptions.

I took this view of the subject. The medulla spinalis has a central division, and also a distinction into anterior and posterior fasciculi, corresponding with the anterior and posterior portions of the brain. Further we can trace down the crura of the cerebrum into the anterior fasciculus of the spinal marrow, and the crura of the cerebellum into the posterior fasciculus. I thought that here I might have an opportunity of touching the cerebellum, as it were, through the posterior portion of the spinal marrow, and the cerebrum by the anterior portion. To this end I made experiments which, though they were not conclusive, encouraged me in the view I had taken. I found that injury done to the anterior portion of the spinal marrow, convulsed the animal more certainly than injury done to the posterior portion; but I found it difficult to make the experiment without injuring both portions.

Nervous messages are invariably associated with an electrical change known as the action potential. This potential is generally believed to arise at a membrane which is situated between the axoplasm and the external medium. If this theory is correct, it should be possible to record the action potential between an electrode inside a nerve fibre and the conducting fluid outside it. Most nerve fibres are too small for this to be tested directly, but we have recently succeeded in inserting micro-electrodes into the giant axons of squids (Loligo forbesi).
Co-author with Andrew Aelding Huxley, British physiologist, (1917- ).

Now, there are a very large number of bodily movements, having their source in our nervous system, that do not possess the character of conscious actions.

On laying bare the roots of the spinal nerves, I found that I could cut across the posterior fasciculus of nerves, which took its origin from the posterior portion of the spinal marrow without convulsing the muscles of the back; but that on touching the anterior fasciculus with the point of a knife, the muscles of the back were immediately convulsed.

One most necessary function of the brain is to exert an inhibitory power over the nerve centres that lie below it, just as man exercises a beneficial control over his fellow animals of a lower order of dignity; and the increased irregular activity of the lower centres surely betokens a degeneration: it is like the turbulent, aimless action of a democracy without a head.

One of the many useful properties of giant nerve fibres is that samples of protoplasm or axoplasm as it is usually called can be obtained by squeezing out the contents from a cut end ... As in many other cells there is a high concentration of potassium ions and relatively low concentration of sodium and chloride ions. This is the reverse of the situation in the animals' blood or in sea water, where sodium and chloride are the dominant ions and potassium is relatively dilute.

Plasticity, then, in the wide sense of the word, means the possession of a structure weak enough to yield to an influence, but strong enough not to yield all at once. Each relatively stable phase of equilibrium in such a structure is marked by what we may call a new set of habits. Organic matter, especially nervous tissue, seems endowed with a very extraordinary degree of plasticity of this sort ; so that we may without hesitation lay down as our first proposition the following, that the phenomena of habit in living beings are due to plasticity of the organic materials of which their bodies are composed.

The cerebrum I consider as the grand organ by which the mind is united to the body. Into it all the nerves from the external organs of the senses enter; and from it all the nerves which are agents of the will pass out.

The doctrine of evolution implies the passage from the most organised to the least organised, or, in other terms, from the most general to the most special. Roughly, we say that there is a gradual 'adding on' of the more and more special, a continual adding on of new organisations. But this 'adding on' is at the same time a 'keeping down'. The higher nervous arrangements evolved out of the lower keep down those lower, just as a government evolved out of a nation controls as well as directs that nation.

The inhibitory nerves are of as fundamental importance in the economy of the body as the motor nerves. No evidence exists that the same nerve fibre is sometimes capable of acting as a motor nerve, sometimes as a nerve of inhibition, but on the contrary the latter nerves form a separate and complete nervous system subject to as definite anatomical and histological laws as the former.

The night before Easter Sunday of that year (1920) I awoke, turned on the light, and jotted down a few notes on a tiny slip of thin paper. Then I fell asleep again. It occurred to me at six o'clock in the morning that during the night I had written down something most important, but I was unable to decipher the scrawl. The next night, at three o'clock, the idea returned. It was the design of an experiment to determine whether the hypothesis of chemical transmission that I had uttered seventeen years ago was correct. I got up immediately, went to the laboratory, and performed a simple experiment on a frog heart according to the nocturnal design. I have to describe this experiment briefly since its results became the foundation of the theory of chemical transmission of the nervous impulse. The hearts of two frogs were isolated, the first with its nerves, the second without. Both hearts were attached to Straub cannulas filled with a little Ringer solution. The vagus nerve of the first heart was stimulated for a few minutes. Then the Ringer solution that had been in the first heart during the stimulation of the vagus was transferred to the second heart. It slowed and its beats diminished just as if its vagus had been stimulated. Similarly, when the accelerator nerve was stimulated and the Ringer from this period transferred, the second heart speeded up and its beats increased. These results unequivocally proved that the nerves do not influence the heart directly but liberate from their terminals specific chemical substances which, in their turn, cause the well-known modifications of the function of the heart characteristic of the stimulation of its nerves.

The question of a possible physiological significance, in the resemblance between the action of choline esters and the effects of certain divisions of the involuntary nervous system, is one of great interest, but one for the discussion of which little evidence is available. Acetyl-choline is, of all the substances examined, the one whose action is most suggestive in this direction. The fact that its action surpasses even that of adrenaline, both in intensity and evanescence, when considered in conjunction with the fact that each of these two bases reproduces those effects of involuntary nerves which are absent from the action of the other, so that the two actions are in many directions at once complementary and antagonistic, gives plenty of scope for speculation.

The result of all these experiments has given place to a new division of the parts of the human body, which I shall follow in this short essay, by distinguishing those which are susceptible of Irritability and Sensibility, from those which are not. But the theory, why some parts of the human body are endowed with these properties, while others are not, I shall not at all meddle with. For I am persuaded that the source of both lies concealed beyond the reach of the knife and microscope, beyond which I do not chuse to hazard many conjectures, as I have no desire of teaching what I am ignorant of myself. For the vanity of attempting to guide others in paths where we find ourselves in the dark, shews, in my humble opinion, the last degree of arrogance and ignorance.

The stimulus of competition, when applied at an early age to real thought processes, is injurious both to nerve-power and to scientific insight.

The true-spinal system consists of a series of nerves passing principally from the cutaneous surface, and the surface of the mucous membranes, to the spinal marrow; and of another series of nerves passing from the spinal marrow to a series of muscles, destined to be moved simultaneously. The former, thence designated the incident nerves; the latter, reflex nerves: the spinal marrow is their common centre.

We come back then to our records of nervous messages with a reasonable assurance that they do tell us what the message is like. It is a succession of brief waves of surface breakdown, each allowing a momentary leakage of ions from the nerve fibre. The waves can be set up so that they follow one another in rapid or in slow succession, and this is the only form of gradation of which the message is capable. Essentially the same kind of activity is found in all sorts of nerve fibres from all sorts of animals and there is no evidence to suggest that any other kind of nervous transmission is possible. In fact we may conclude that the electrical method can tell us how the nerve fibre carries out its function as the conducting unit of the nervous system, and that it does so by reactions of a fairly simple type.

We have learned that there is an endocrinology of elation and despair, a chemistry of mystical insight, and, in relation to the autonomic nervous system, a meteorology and even... an astro-physics of changing moods.

We have seen that the cytoplasm of nerve has a fluid consistency. Hence its molecules are free to move. According to the thermodynamic principle known as the Gibbs-Thompson rule, any substance in the interior of a liquid which will reduce the free energy of the surface of the liquid, will be concentrated in the surface. The composition of the surface is, therefore, determined by the composition of the fluid from which it is formed; and as the rule is one having universal application, it must hold also for the cytoplasm of nerve. We must think of the surface membrane, then, as a structure which is in equilibrium with the interior of the axon, or at least as one which deviates from equilibrium only because, for dynamic reasons, equilibrium cannot be attained.
With Joseph Erlanger (1874-1965), American physiologist.

When external objects are impressed on the sensory nerves, they excite vibrations in the aether residing in the pores of these nerves... Thus it seems that light affects both the optic nerve and the aether and ... the affections of the aether are communicated to the optic nerve, and vice versa. And the same may be observed of frictions of the skin, taste, smells and sounds... Vibrations in the aether will agitate the small particles of the medullary substance of the sensory nerves with synchronous vibrations... up to the brain... These vibrations are motions backwards and forwards of small particles, of the same kind with the oscillations of pendulums, and the tremblings of the particles of the sounding bodies (but) exceedingly short and small, so as not to have the least efficacy to disturb or move the whole bodies of the nerves... That the nerves themselves should vibrate like musical strings is highly absurd.

Why may we not say, that all Automata (Engines that move themselves by springs and wheeles as doth a watch) have an artificiall life? For what is the Heart, but a Spring; and the Nerves, but so many Strings; and the Joynts, but so many Wheeles, giving motion to the whole Body, such as was intended by the Artificer? Art goes yet further, imitating the rationall and most excellent worke of Nature, Man. For by Art is created the great LEVIATHAN called a COMMON-WEALTH, or STATE, (in latine CIVITAS) which is but an Artificiall Man; though of greater stature and strength than the Naturall, for whose protection and defence it was intended; and in which, the Soveraignty is an Artificiall Soul, as giving life and motion to the whole body.