Capítulo de la edición 25 aniversario de "Fundations of the Neuron Doctrine", la clásica obra sobre la 'Doctrina Neuronal" del Profesor en Neurociencia de la Universidad de Yale: Gordon Shepherd.

3. 7
The Nerve Cell Studies of Freud
Although Gerlach gave a new level of credibility to the reticular idea, there were
many microscopists in the 1870s who were relatively unswayed by such
theoretical considerations and simply pushed forward in the attempt to see more
clearly the nerve cell and its relation to nerve fibers. As noted in the previous
chapter, one of these was Sigmund Freud. His neuroanatomical work early in his
career is of particular interest because of the claim by several of his biographers
that it led him to the brink of the neuron doctrine (Brun, 1936; Jelliffe, 1937; Jones,
1953). These studies are also of interest because they were the first step in the
scientific career pursued by Freud before he began the work that led to his
theories of psychoanalysis. We will briefly review the aspects of his early work
that directly concern the structure and organization of nerve cells (see Jelliffe,
1937; Bernfeld, 1944; 1947; 1950; 1951 Jones, 1953; Amacher, 1965), and end
with a brief consideration of his desperate attempt at a synthesis.
THE YOUNG STUDENT
Freud, the son of a wool merchant, was born in 1856 in Freiberg, now Pribor,
Czechoslovakia. The family moved to Vienna in 1860, where Freud grew up in
rather straitened circumstances. Being Jewish, of a nonacademic family, and
impecunious were considerable obstacles to an academic career in nineteenth-
century Europe. However, there was always a chance for a youth if he had talent,
ambition, and persistence (recall Remak, Chapter 2). Freud entered medical
school in Vienna in 1873. Drawn toward biology, he spent the summer of 1876 in
the new Zoological Station in Trieste on the Adriatic. He engaged in several
attempts at anatomical research, with little satisfaction, and his studies were
moving at a desultory pace until he met Professor Ernst von Brucke.
When last we encountered Brucke he was one of the four zealous young students
in Germany in the 1840s determined to rebuild the field of physiology on the laws
of chemistry and physics (see Chapter 3). He had come to Vienna in 1849 as
professor of physiology (his friends teased him that he was their “ambassador to
the Orient”).
As mentioned previously, he had broad interests in a range of physiological
processes.
Unlike many physiologists, he found it quite natural to pursue microscopical
studies as well. Over the years his Institute of Physiology gained considerable
fame; however, as with others we have met (Purkinje, Chapter 2), or will meet
(Meynert, Chapter 9), the institute was poorly equipped (Jones, 1953):
The Institute was miserably housed in the ground floor and basement
of a dark and smelly old gun factory. It consisted of a large room where
the students kept their microscopes and listened to lectures, and two

4. smaller ones, one of which was Brucke’s sanctum. There were also on
both floors a few small cubicles, some without windows, that served
as chemical, electrophysiological, and optical laboratories. There was
no water supply, no gas, and of course no electricity. All heating had
to be done over a spirit lamp, and the water was brought up from a
well in the yard where also a shed housed the animals experimented
on. Nevertheless this Institute was the pride of the medical school on
account of the number and distinction of its foreign visitors and
students.
In his Autobiographical Study, Freud’s description of how he began his
neuroanatomical studies under Brucke is succinct to the point of perfunctory
(Freud, 1935/1952):
At length in Ernst Brucke’s physiological laboratory, I found rest and
satisfaction—and men, too, whom I could respect and take as my
models: the great Brucke himself, and his assistants Sigmund Exner
and Ernst von Fleischl-Marxow. Brucke gave me a problem to work
out in the histology of the nervous system; I succeeded in solving it to
his satisfaction and in carrying the
work further on my own account.
This cryptic passage has suggested that Freud came to his studies of nerve cells
with no great passion for them, but simply with the resolve to “work out” the
problem set for him by the great master. It was not that he did not enjoy the work,
for he looked back on these years as the happiest of his life.
NERVE CELLS AND FIBERS IN A PRIMITIVE FISH
The problem Brucke gave to Freud was to clarify the structure of a particular large
type of nerve cell, discovered by Reissner, that is situated in the spinal cord of a
fish, Petromyzon, belonging to the cyclostomata. This is a primitive vertebrate
species, and therefore has always been of interest for the insights it can give into
early vertebrate evolution. Within a few weeks (Jones, 1953), Freud reported to
Brucke that he could not only trace peripheral sensory nerves to their origins from
Reissner’s cells, but he could also see fibers in the dorsal (sensory) roots that
arose from these same cells and passed centrally into the spinal cord. This led to
his first scientific papers (Freud, 1877, 1878), in which he concluded that
Reissner’s cells “are nothing else than spinal ganglion cells which, in those low
vertebrates, where the migration of the embryonic neural tube to the periphery is
not yet completed, remain within the spinal cord.”
Although he subsequently found in searching the literature that this had been
described by a Russian investigator some years before, it was nonetheless a
significant study. His further observations led him to an even more interesting
conclusion:
The spinal ganglion cells of the fish have long been known to be
bipolar . . . while those of the higher vertebrata are unipolar. . . . The

5. nerve cells of the Petromyzon show all transitions from uni- to
bipolarity.
In other words, the observations in Petromyzon enabled one to construct an
evolutionary sequence for dorsal root ganglion cells, from the bipolar form, to
transitional forms that are either bipolar or unipolar, to strictly unipolar forms as
seen in the higher vertebrates. We do not know how much of this synthesis came
from Freud and how much from his three mentors, but it is likely that Freud drew
both inspiration and ideas from Brucke, who had a very broad view of anatomical
structure and physiological processes. We will see that the unipolar form of the
dorsal root ganglion cell posed a difficult problem for later workers seeking to
embrace all nerve cells in one functional framework (see Chapter 15).
NERVE CELLS AND FIBERS IN CRAYFISH
Freud next took up, “on his own account,” according to his autobiography, a study
of nerve cells in the crayfish. This was published in 1882 as an article entitled
“Uber den Bau der Nervenfasen und Hervenzellen beim Flusskrebs” (“On the
structure of nerve fibers and nerve cells of the crayfish”). It consisted of 37 pages,
accompanied by a plate of five illustrations carefully drawn by himself (Fig. 9).
We will quote at some length from this article, because it represents Freud’s most
mature work on the microscopic structure of nerve cells. The first paragraph
introduces the subject and the reasons for selecting the crayfish:
The observations presented here were started in the summer months
of 1879 and 1881 in the hope of advancing the understanding of the
finer structure of nervous tissue by studying, where possible, fresher
surviving elements. As . . . this task encounters far too great difficulties
in the vertebrates, I have put my confidence in the general significance
of results obtained in invertebrates, and chose from these, being most
accessible to me, the crayfish, in which animal the size and the looser
connections of elementary parts, as well as the generous presence of
an apparently protective supplementary fluidity in the blood, promised
to ease the research.

6. Figure 9 Illustrations of nerve cells by Sigmund Freud. “(1). Nerve cell from the tail ganglion of
the crayfish which (joins with) the cell peripherally. In the nucleus, besides the roundish nuclear
bodies are several short thick small rods and a nuclear figure consisting of two parts. Drawn by
Hartnack 3/8. Magnification of the drawing 360. (2). Surviving nerve cell from an abdominal
ganglion with cone shaped arising extension. In the nucleus, which does not have a nuclear
membrane, are four multipointed small clusters and one long rod bent and forked at one end. At
k is a nucleus of the covering sheath. The same magnification. (3). Border section from the spindle
shaped stomatogastric ganglion of the crayfish. Two unipolar nerve cells with their extensions of
which one undergoes a T-shaped division. The smaller cell is indicated by a focus near the
surface. s The thick, concentric layered cell sheath. ks The nucleus itself. hm Strong, shiny
homogeneous mass at the edge of the cell, yet situated inside the covering sheath. f A fiber
coming from another cell. The same magnification. (4). The nucleus of a large nerve cell which
showed suggestions of movement on both kinds of nuclear bodies, b is drawn five minutes later
than a. Hartnack 3/x. Magnification of the drawing 400. (5). A portion of a cell with extension as
in (1) In the nucleus a large number of neatly forked and bent (small) rods. The same
magnification as in (4).” (Freud, 1882)
After a thorough presentation of his observations, Freud drew his conclusions
concerning the internal structure of the nerve cells:
The results of my observations of the nerve cells of the crayfish may
be summarized as follows: The nerve cells in the brain and in the
stomatic ganglionic chain consist of two substances, of which one,
arranged in a netlike fashion, extends into the fibrils of the nerve fibers,
whereas the other goes into the ground substance. . . . The nucleus of
the nerve cell consists of a homogeneous mass, not sharply defined
at the boundary with the cell body, in which formations of various
shapes and durability are visible. These nuclear bodies show changes
in shape and location which reflect the conditions of survival of the cell.
This conclusion is entirely consistent with Deiters’ description of the origin of the
axis cylinder from the nerve cell body (Chapter 4). The paper ends with a more
general discussion of the significance of these findings:
The nerve cell up to this point does not show any unique structural
aspects; its function is consistent with the general structure of the
animal cell as far as this can be determined (Brucke, 1861). However,
this does not permit any conclusion to be drawn as to a higher or lower
physiological dignity of the nerve cell.
I remind you that there is no reason to assume that the relationship of the nerve
cell to the nerve fiber is any different in the invertebrates from that in the
vertebrates. Waldeyer has stated that the extensions of the large central nerve
cells of invertebrates never become peripheral nerve fibers, but instead go into
the central substance of the ganglion where they dissolve into fine fibrils and that
on the other side the peripheral nerve fibers originate by the coming together of
fibrils of the central substance. It was obvious to add a further assumption to this,
that in an invertebrate nerve fiber, fibrils belonging to different nerve cells come
together.
Leydig’s . . . view differs from that of Waldeyer’s, in that he sees a direct transition
of extensions of central nerve cells into nerve fibers, which would do away with

7. the stated difference by Waldeyer between the nerve tissue of invertebrates and
vertebrates. In the vertebrates, as we know, the direct transition of cell extensions
in peripheral nerve fibers has been shown for the cells of the central organ, and
Deiters himself has indicated signs by which the axis cylinder, already at its origin
from the nerve cells, is recognizable. However, it has not been ascertained
throughout in the vertebrates that all nerve fibers are interconnected with nerve
cells in the same way. It is moreover possible that here, too, nerve fibers originate
from a central fiber mass and that a peripheral fiber contains fibrils of different
origins and significance. This relationship has neither been proven for the
invertebrates nor disproven for the vertebrates.
Several findings moreover support an even deeper agreement of the nerve tissue
of the two large animal classes on this point. In the Phrominides, a family of water
flea, Claus, in experiments on the stomatic ganglionic chain, has found in
longitudinal sections that the extensions of the large nerve cells pass directly into
the fibers of the nerve trunk—indeed, mostly into those crossed, with some on
the same side. Claus goes so far as to assume that most of the large cells of the
stomatic ganglionic chain are multipolar.
A number of multipolar cells are now known with certainty to be present in the
central nervous systems of crustacea, as it appears in Claus’ pictures and from
my isolated preparations. Moreover, the multipolar cells which I have presented
in the crayfish show, as already indicated, each of the characteristics in their
extensions which Deiters set forth to differentiate between axis cylinder—and
protoplasma—continuations. Concerning the low number of cells of Deiters in the
crayfish, it must be remembered that in the vertebrates as well, presumably only
certain groups of cells are constructed according to Deiters’ schema.
FINAL THOUGHTS ON NERVE CELLS
Within the year after the crayfish paper appeared, Freud delivered a lecture to
the local Psychiatric Society, which was published in 1884 under the title “The
structure of the elements of the nervous system.” His views on the general
question of the relation between nerve structure and nerve functions are summed
up in the following passage (cited in Jones, 1953):
If we assume that the fibrils of the nerve have the significance of
isolated paths of conduction, then we should have to say that the
pathways which in the nerve are separate are confluent in the nerve
cell: then the nerve cell becomes the “beginning” of all those nerve
fibers anatomically connected with it. . . . I do not know if the existing
material suffices to decide the problem, so important for physiology. If
this assumption could be established it would take us a good step
further in the physiology of the nerve elements: we could imagine that
a stimulus of a certain strength might break down the isolation of the
fibrils so that the nerve as a unit conducts the excitation, and so on.
This was an interesting conclusion. Freud here was emphasizing the possible
role of the neurofibrils within the nerve fibers in conducting nervous activity. This
was an erroneous view, kept alive by anatomists; physiologists by that time knew

8. pretty well that the nerve impulse was a membrane property, that is, the impulse
spreads along the outer membrane of the nerve, without any involvement of
internal structures beyond their providing a pathway for intracellular current. On
the other hand, the idea of pathways becoming confluent in the cell body was an
echo of Deiters (Chapter 4) and anticipated Sherrington’s concept of the nerve
cell as a final common path (see Chapter 17). It is interesting in this regard that
Sherrington himself was much influenced by Exner (see Sherrington, 1906), who
was one of Freud’s mentors in Brucke’s laboratory. Freud’s reference to “the
nerve as a unit” in the conduction of activity is also an echo of Deiters, and is an
early instance of that phrase in the literature. It suggests that he, and perhaps his
colleagues, were beginning to think in general terms of the nerve cell as an
anatomical and functional unit. Unfortunately, the specific kinds of mechanisms
that might be mediated by this unit are contained in the final phrase “and so on”!
THE SIGNIFICANCE
OF FREUD’S MICROSCOPICAL STUDIES
Several of Freud’s biographers have suggested that his work made a direct
contribution to the neuron doctrine. Thus, according to Jelliffe (1937):
Freud maintained the essential similarities of the nervous tissues and
functions in invertebrates and in vertebrates which in his day was not
the generally held opinion. Thus he may correctly be said to have
grasped the significance of the neuron theory net work, from his
studies on the living tissues of the fresh water crab [sic].
The generalization of results between invertebrates and vertebrates was a valid
contribution, but it was neither new nor unique; we have seen that the idea that
invertebrates were useful in this respect began with Helmholtz and Kolliker in the
1840s and Leydig in the 1850s. Just what is meant by the “neuron theory net
work” is not at all clear. Jelliffe translates Flusskrebs as “fresh water crab.” The
dictionary translation is “river crayfish,” and most authors have translated it as
“crayfish” (cf. Amacher, 1965; Jones, 1953).
A more persuasive case is argued by Ernest Jones. This is perhaps not
surprising, given that Jones was chairman of the “Committee” that during Freud’s
lifetime passed judgment on the purity of doctrine in the psychoanalytic
movement; he was in addition the author of the first comprehensive biography of
Freud (Jones, 1953). With regard to Freud’s observations on the continuity of
nerve cell body and axis cylinder, he states that Freud was the first to
demonstrate that axis cylinders “are without exception fibrillary in structure”
(Jones, 1953). We have seen that many workers had been intrigued by the fibrils
contained in nerve fibers. This became a frequent topic of investigation around
1880 as new stains and improved microscopic techniques allowed better
visualization of the internal structure of nerve cells (see Chapter 14). Freud
certainly made a solid contribution in that progress toward the new field of
cytology.
With regard to the significance of Freud’s work for the neuron doctrine, Jones
sums up his judgment as follows:

9. With this paper [on the crayfish] and the two preceding ones [on
Petromyzon] Freud had done his share to pave the way for the
neurone theory. One might safely go even a little further and claim, as
have Brun (1936) and Jelliffe (1937), that Freud had early and clearly
conceived the nerve cells and fibrils to be one morphological and
physiological unit—the later neurone. . . .
After discussing Freud’s final overview in 1884, quoted above, Jones further
comments:
This unitary conception of the nerve cell and processes—the essence
of the future neurone theory—seems to have been Freud’s own and
quite independent of his teachers at the Institute. There is certainly in
his few sentences a boldness of thought and a cautiousness in
presentation; he makes no real claim. But two comments seem in
place. The lecture containing those remarks was delivered four or five
years after he had conducted the researches on which they were
based, so that the period of rumination was a long one. Then, after so
much time for reflection, one would have thought that a little of the free
and bold imagination he was so often to display in later years would
have carried him the small step further, for he was trembling on the
very brink of the important neurone theory, the basis of modern
neurology.
In the endeavor to acquire “discipline” he had not yet perceived that in
original scientific work there is an equally important place for
imagination.
Actually no notice was taken of these precious sentences, so that
Freud’s name is not mentioned among the pioneers of the neurone
theory. . . . It was not the only time that Freud narrowly missed world
fame in early life through not daring to pursue his thoughts to their
logical—and not far-off—conclusion.
FROM NERVE CELLS TO NEUROLOGY
TO “PROJECT FOR A SCIENTIFIC PSYCHOLOGY”
Freud received his M.D. degree in Vienna in 1881. Although he appeared to be
ready for a career of laboratory investigation on the histology of nerve cells, his
prospects for an academic position were poor because Brucke had not just one
but two heirs apparent, Exner and von Fleishl-Marxow, both relatively young and
very able. In 1882, Brucke advised Freud, in view of Freud’s “bad financial
position,” to “abandon his theoretical career” (Freud, 1935/1952). Freud seems
to have accepted this advice without discussion, and forthwith became a junior
resident physician in the main General Hospital in Vienna. Here he began
specialization in neurological disorders; also, under Meynert, he pursued
microscopical studies of nerve tracts in the human brain, especially the hind brain
(medulla oblongata).
In 1885, Freud submitted his application for the position of Privatdozent, which
was essential for continuing his professional and academic career. The research
accomplishments that he included in the application rested on his microscopical

10. studies of nerve cells under Brucke and of nerve tracts in the medulla under
Meynert, and clinical studies of a case of cerebral hemorrhage (see Jones, 1953).
He had also initiated experiments on the behavioral effects of cocaine (see Byck,
1974). He was successful in his application, and successful as well in obtaining
in the same year a travel grant to study under the great neurologist, Charcot, in
Paris. With his professional future at last assured, he married in 1886 (Fig. 10).
For the next several years he was absorbed in his work in clinical neurology. His
earlier microscopical work, especially on the origin of dorsal root fibers, was
usually referenced by the later workers whose studies led to the neuron doctrine
(see Chapters 9–14). In 1891, the same year in which the neuron doctrine was
promulgated, he published a book on aphasia. From that time he moved step by
step toward his theory of psychoanalysis, through the studies of hysteria (1895),
dreams (1899), and sexuality (1905).
It might be assumed that during this period he had turned his back on the studies
of the nerve cell; for example, the subject of the neuron doctrine receives no
mention in his Autobiography. But the influence of his early neuroanatomical
training was not to be shaken so easily. In 1895 Freud tried to put his emerging
psychological concepts on a mechanistic basis by writing “Project for a Scientific
Psychology,” drawing on everything he had learned about nerve cells and brain
structure from Brucke and Meynert, as well as from keeping up on the work
leading to the neuron doctrine. His hope, which would seem to have gone straight
back to Brucke’s early vow in the 1840s, was to define how nerve cells and their
mechanistic states of energy could generate quantitatively determined psychical
processes.
Figure 10 Sigmund Freud and Martha Bernays, in 1885, the year before they were married.
(From Jones, 1953)

11. The “project” was a long manuscript in German assembled from many loose
pages and only published in the final compilation of his papers (Freud, 1953). It
produced one diagram, shown in Fig. 10A.
Figure 10A Diagram in Fig. 14 from Freud (1953) illustrating the possible relation between
neurons, neuronal connections, junctional (synaptic) properties, and “psychical primary
processes” (see text).
Although it is usually regarded as evidence of his failure to draw the
neuroanatomy of the mind, it deserves more careful consideration for the insights
into Freud’s mind and as a reflection of the state of knowledge at that time. Freud
begins with a section on “The Neurone Theory.” At this critical point in Freud’s
career, he was struggling to represent “real” neurons, as he knew them as a
neuroanatomist, with physiological properties (still unknown), and relate them to
the behavioral scheme he was formulating. The neurons are oversimplified, but
they have extensions representing axons and dendrites, and they are
interconnected by what he called “contact barriers.” (Two years later Sherrington
named them “synapses”). Since there was no known physiology of central
neurons, he had to think them up. A “primary neuronic system” has quantities of
charge, which it is constantly trying to discharge (he suggests the term “cathexis”
in this physiological sense). The “charge” in each neuron gives rise to current
flows through the branches in relation to how much “resistance” there is. “Thus,”
he writes, “the course taken depends on the quantities (Q) and the relative
strength of the facilitations.” Writing in relation to the diagram in Fig. 10A, he
conceives that
. . . “lateral” cathexis thus acts as an inhibition on the passage of
quantity Q. Let us imagine the ego as a network of cathected
neurones, well facilitated in relation to one another [see figure]. Then
suppose a quantity (Q’~) enters neurone a from the outside (<D). If it
were uninfluenced it would have proceeded to neurone h. But it is in
fact so much influenced by the lateral cathexis in neurone o that it only
passes on a quotient to b, or may even not reach b at all. Where, then,
an ego exists, it is bound to inhibit psychical processes.
This is only a brief extract from a manuscript that runs to over 100 pages (Freud,

12. 1953). After several months of feverish effort he gave up the project in despair; it
was not published in his lifetime. However, according to his biographer (Gay,
1989), “he never abandoned his ambition to found a scientific psychology.”
Previous scholars have analyzed many aspects of his early scientific training (cf.
Brun, 1936; Bernfeld, 1951; Amacher, 1965). Some scholars have suggested that
Freud’s concepts of neural mechanisms of learning and memory anticipated long-
term potentiation (LTP) and the concepts of Hebb (Centonze et al., 2004). With
its unique vocabulary and mixture of anatomical and psychological terms and
concepts, it seems a very preliminary attempt at describing the neural basis of
psychology. It would appear that there is a rich field here for analyzing more
specifically how Freud’s studies of nerve cells found their way—consciously and
unconsciously—into his concepts of normal and pathological mental processes.