Journal of the History of the Neurosciences 0964-704X/99/0802-209$15.

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1999, Vol. 8, No. 2, pp. 209–214 © Swets & Zeitlinger

The Legacy of Camillo Golgi for Modern Concepts

of Brain Organization*
Gordon M. Shepherd
Section of Neurobiology, Yale University School of Medicine, New Haven, USA

ABSTRACT

The experimental advance made by Camillo Golgi’s ‘black reaction’ has been universally recognized as
the start of the modern revolution in the study of the nervous system. By contrast, his concepts of nervous
organization, particularly his support for the idea of a ‘nervous reticulum’, have been universally rejected.
The premise of the present paper is that the ideas of a biologist of this stature deserve re-examination.
Golgi’s arguments for considering the holistic function of the brain seem to come from his experience as
a physician, and presage the views of the gestaltists and, more recently, the conceptual underpinnings of
artificial neural networks. His interest in the possible nutritional roles of neuronal dendrites can be seen to
anticipate current investigations, at the cellular level, of the metabolic basis of brain imaging. These and
other currents in Golgi’s thought deserve further study.

The scientific accomplishments of Camillo
Golgi have been acknowledged since the Golgi
stain became known to neuroanatomists in the
1880s. When the methods for the ‘black reac-
tion’ became established and reliable in the
1890s, they fuelled the fundamental break-
through in laying the cellular basis of brain or-
ganization, which in turn was the foundation for
the rise of modern neuroscience. The ‘black re-
action’ gained Golgi the highest recognition
among his peers, as evidenced by the award of
the Nobel Prize in 1906. Taken together with his
pioneering studies of the cellular basis of ma-
laria in the 1880s and his description in 1898 of
the intracellular body that now bears his name,
his discoveries rank him among the greatest bi-
ologists of all time (see Mazzarella, 1996).
In contrast to his experimental work, Golgi’s
ideas – especially his belief that neurons form a
continuous nervous network through their cell
processes – were rejected by the majority of the
neuroanatomists of that time. His unbending
defense of neuronal continuity in his Nobel lec-
ture in 1906 only served to further discredit the
idea. After the demonstration of discontinuity
between cells at chemical synapses by the pio-
neering electronmicroscopical and electrophy-
siological studies of the 1950s, Golgi’s ‘nervous
reticulum’ became a cliché for outmoded ideas
consigned to the scrap heap of history.
In the present age, when many investigators
view history as something that happened last
year, or last month, it seems that there is little to
be gained from considering discredited ideas
like these a century or more out of date. And yet
– perhaps the ideas of one of history’s greatest
biologists deserve a second look.
The occasion for doing this occurred for the
present author during a review of the work that
led to the establishment of the neuron doctrine
(Shepherd, 1991). The principle adopted for that
review was to examine the earliest papers of the
different pioneers, in order to capture as much
as possible the essential results and ideas that
they contributed as close as possible to the mo-
ments of creation. That is when the ideas are

*
Address correspondence to: Dr. G.M. Shepherd, Section of Neurobiology, Yale University School of Medicine,
333 Cedar Street, New Haven, CT 06510, USA. Tel.: +1 203-785-4336. Fax: +1 203-785-6990. E-mail: gordon.
shepherd@yale.edu.
210 GORDON M. SHEPHERD
fresh and presented in their purest form with the
motivation to persuade skeptical colleagues of
the validity of a new way of thinking about a
field of knowledge. As time goes by, the results
become superseded by more sophisticated ex-
periments and the ideas become encrusted with
derivative explanations, apologias, or attacks on
competing explanations.
This way of judging the essence of a scien-
tist’s contributions is similar to Claude Ber-
nard’s view of how to assess the significance of
scientist’s career. As expressed in his testimo-
nial to his mentor, François Magendie (in
Grmek, 1973, p. 21; from Bernard, François Ma-
gendie, p. 3): ‘Quand on veut juger l’influence
qu’un homme a eue sur ses contemporains, ce
n’est point à la fin de sa carrière qu’il faut le
considerer, lorsque tout le monde pense comme
lui; c’est au contraire à son début qu’il faut le
voir, quand il pense autrement que les autres.’
(‘When one wants to judge the influence that a
man has had on his contemporaries, it is not at
the end of his career, when all the world thinks
as he does, that one should look; on the contrary,
it is at the beginning, when he thinks differently
from the others.’)
Golgi seems a special instance, a kind of in-
verted version, of Bernard’s dictum: in the be-
ginning his method allowed him to think differ-
ently from the others, but the same method al-
lowed the others to think differently by the end.
At this time of the centennial of Golgi’s semi-
nal contribution to cytology – the demonstration
of the Golgi apparatus – it seems appropriate to
pursue further this inquiry into the nature of
Golgi’s ideas about nervous organization. We
will first identify his experimental findings that
have stood the test of time. For this purpose I
wish to focus on the application of the black re-
action to nerve cells in the central nervous sys-
tem. In doing so we leave aside many other fun-
damental contributions, such as the Golgi body,
the studies of fibrous and protoplasmic astro-
cytes, the perineuronal reticulum, and the de-
scription of the tendon organ that bears his name
(for these subjects, see articles in this volume).
We then consider more deeply how these find-
ings led him to his concepts of brain organiza-
tion. The thesis advanced here is that the find-
ings themselves are more profound than we usu-
ally realize, and the ideas in fact have a surpris-
ing relevance for current concepts of neural net-
works.
GOLGI’S DISCOVERIES AND THEIR REL-
EVANCE FOR TODAY
Golgi’s discoveries with his ‘black reaction’
may be summarized as follows (Golgi, 1873,
1883a, 1886). The nerve cell was revealed in its
entirety for the first time. One could differenti-
ate clearly between the axis cylinder (which we
now call axon) and the other processes arising
from the cell body (which we now call den-
drites). Golgi correctly deduced the rule that if a
neuron has an axon, it typically has only one. He
emphasized that this axon was the means for
transmission between regions, thus making the
crucial distinction with Gerlach’s emphasis on
fibers arising from dendritic networks.
The discovery that Golgi himself seemed to
prize the most, and which formed the basis for
his ideas regarding nerve nets, was the discovery
of collateral branches that arise from axons near
their origin. He proposed that all nerve cells can
be divided into two types on the basis of their
axons and axon collaterals. What came to be
called Golgi’s Type I cells have a long axon that
gives off branching collaterals locally before
leaving that region to connect to distant regions;
we now call these relay cells or principal neu-
rons. Type II cells have short axons that branch
within the region of origin to give rise to a sys-
tem of local branches that remain within that
region; we now call these local neurons or
interneurons. Finally, he observed clearly that
each region contains different types of long and
short axon cells, on the basis of their patterns of
dendritic and axon collateral branching, and he
characterized many of these types for the first
time.
In his drawings, Golgi represented the differ-
ent types of neurons and their relations with
each other in a distinct artistic style, which one
might characterize as fin de siècle art deco.
While these stylized drawings had a great artis-
tic beauty, they were rapidly superseded by the
 GOLGI’S LEGACY
coarser but more biologically realistic drawings
of his contemporaries and subsequent scholars.
However, it is obvious that most of our basic
concepts regarding the outward morphology of
neurons can be traced back to Golgi.
The Golgi method was not only the first
method for visualizing an entire nerve cell, it
was the only method for most of the following
century. Not until the 1960s was the first injec-
tion of dyes through intracellular electrodes
achieved by Stretton and Kravitz (1968), fol-
lowed in the 1970s by HRP injections (cf. Kitai,
1981). The present author remembers vividly the
impact of those developments: the opportunity
for the first time of correlating the morphology
of the cell from which recordings were obtained,
and the dramatic revelations by HRP staining of
the tremendous branching of small dendrites and
collateralization of axons. The Golgi method
was therefore the forerunner of the wide range
of methods for single cell staining that are es-
sential for much of modern neuroscience at the
cellular level.
GOLGI’S IDEAS AND THEIR RELEVANCE
FOR TODAY
Based on his findings, Golgi deduced several
general concepts about the organization of the
individual neuron and its interactions with other
neurons. A remarkable aspect of these concepts
is that most of them are expressed in his very
first report of the method (Golgi, 1873). They
were all formulated and published by the early
1880s (see Golgi, 1883a,b), well before his
method became known to the rest of the world
through publication of translations of his basic
papers (Golgi, 1886). Golgi maintained these
ideas throughout his life. He was the type of sci-
entist who adheres steadfastly to the ideas of his
seminal work. For the rest of his career, Golgi
resisted all new evidence suggesting a revision
of these concepts, while citing among new work
the evidence that appeared to support his views.
Here I should like to focus on three of those
ideas.
211
The Axon Is the ‘‘Neural’’ Part of the Neuron
The first idea was that the axon is the chief part
of the nerve cell responsible for transmitting
nervous signals and carrying out, together with
the axon collaterals, the ‘‘neural’’ functions of
the nerve cell. The fact that axons, as compris-
ing the fibers of the peripheral nerves, transmit
impulses was determined by physiologists by
the middle of the nineteenth century, and it
seemed reasonable to extend this to the axons of
the central nervous system when these pathways
were identified by anatomists later in the cen-
tury. Since impulse transmission was the only
cellular property that had been identified in neu-
rons to that time (synaptic potentials were not
detected until late in the 1930s), there were
many in Golgi’s time who held to the conserva-
tive view that impulse transmission was the only
function of nerve cells, and the axon was obvi-
ously the part of the neuron responsible for this
function. The power of this view can be seen in
the remarks in 1893 by Edward Schäfer on the
term ‘neuron’ introduced by Waldeyer (1891):
The processes [of a nerve cell] are of two
kinds. The first and only essential kind [ed.
italics] is that which has long been known as
the axis-cylinder or nerve-fibre process (Dei-
ters). It is also the first kind to show itself in
the course of development of the nerve cell
[ed. His, 1889]. The other kind is that which
was distinguished by Deiters as the protoplas-
mic process. This is not so essential, for we
find many nerve-cells destitute of it.
Having thus defined the axon as the most impor-
tant part of the nerve cell, Schäfer went on to
introduce his own definitions to recognize this
importance:
The above terms have been long in use to in-
dicate these two kinds of processes, but they
are obviously inconvenient from their length
and from the assumptions which they appear
to imply. I propose therefore to term the axis-
cylinder or nerve-fibre process neurons, and
the protoplasmic processes dendrons.
212 GORDON M. SHEPHERD
These quotations indicate ideas that were preva-
lent at the time. Schäfer had been one of the
founders of The Physiological Society in 1876
(at the age of 26), and author of The Essentials
of Histology in 1885, which was to go through
16 editions. His remarks were made in his Presi-
dential Address to the annual meeting of the
Neurological Society in London. We may take
them therefore as being delivered with the voice
of authority.
These remarks seem closely in line with
Golgi’s belief in the importance of the axons
and axon collaterals for ‘neural functions’
(though Schäfer believed in terminal ramifica-
tions of the axonal branches, not a syncytium).
Golgi himself provided no direct evidence bear-
ing on this issue, but the idea was central to his
conceptual framework. It was essentially a con-
servative view, which we may surmise was ar-
rived at by a sequence of simple logical steps, to
whit: The only available evidence regarding
‘nervous’ properties was the impulse in periph-
eral axons; it was reasonable to hypothesize that
central axons also supported impulses; it was
further reasonable to hypothesize that impulses
were supported by the axon collateral branches
that Golgi had discovered.
We now know that the function of axons and
axon collaterals in transmitting impulses is
nearly universal. However, it should be noted
that modern work has shown that there are ex-
ceptions, for example, the long thin axon con-
necting a type of horizontal cell body with its
terminal axonal arborization is presumed to be
passive, separating the cell body and terminal
axons into separate functional compartments
rather than connecting them by impulse propa-
gation (see Nelson et al, 1976). Proof that action
potentials are supported by all axonal branches
and terminals of local neurons, such as the ex-
tensively ramified axon collaterals of Golgi cells
in the cerebellum, is still lacking.
From Nervous Reticulum to Neural Networks
Golgi’s conclusion that the finest branches of
axons and axon collaterals are continuous led
him to propose that these interconnections form
a diffuse nervous network within the grey matter
of the brain. He proposed to call it a ‘nerve or-
gan’, to which ‘every nerve element of the cen-
tral nervous system contributes’ (Golgi, 1883a).
He considered it to be a distinct anatomical en-
tity, the importance of which was that it permit-
ted ‘group action of nerve cells’ in opposition to
‘their alleged individual action’. Within this dif-
fuse network, ‘the greatest complication of rela-
tions is effected’. Because of this, there is ‘no
anatomical support’ for the functional concept
of ‘isolated transmission’ or, strictly-speaking,
‘localization of cerebral function’ (Golgi,
1883a). (This view was tempered by the ac-
knowledged importance of the localization of
motor function to the motor cortex shown by
Fritsch and Hitzig, which was then fresh. While
acknowledging the importance of this physio-
logical localization at the level of cerebral con-
volutions, Golgi denied that anatomists such as
Betz had provided any anatomical basis for it
(Golgi, 1883b)).
I should like to propose that the interest of
these ideas of a diffuse nervous reticulum for a
modern neuroscientist is not so much in their
anatomical basis, because there is no doubt that
nerve cells anatomically are cellular units, but in
the conceptual framework they provide for un-
derstanding higher brain functions. Golgi be-
lieved from the start in the holistic function of
the nervous system. I suggest that, in a curious
way, the results of the ‘black reaction’ made
only a relatively small contribution to that be-
lief. The fact that the fine collaterals appeared to
him to disappear into a continuous network pro-
vided a convenient framework for his holistic
concept, but he believed in that concept of brain
function regardless of its cellular basis. This is
one reason why he was so elusive on this issue.
What mattered to him were the functional con-
cepts, such as the diffuse reticulum rather than
detailed localization, and prevalent or elective
paths of transmission rather than isolated trans-
mission. And what he most objected to was
anatomists, such as Cajal or Betz, claiming that
their staining of nerve cells, especially when it
was with his stain (!), provided anatomical evi-
dence opposed to those functional views.
While the neuron doctrine has been the un-
derpinning of experimental neuroscience and
clinical neurology for the past century, Golgi’s
 GOLGI’S LEGACY
concept of the network basis for higher brain
function has had its own interesting history. Cer-
tainly when Gestalt psychology, with its empha-
sis on the way we conceive of perceptions in a
holistic manner, became more popular in the
early twentieth century it was in this tradition.
When McCulloch and Pitts in 1943 proposed
that nerve cells are interconnected to form logic
operators, they initiated an emphasis on net-
works of axonal interconnections with an exclu-
sion of dendrites from neural functions, just as
Golgi believed. This led to the development of
perceptrons and ultimately to the computational
‘neural’ networks of today (see Rumelhart and
McClelland, 1986) in which every node
(claimed to represent an entire neuron) is con-
nected by means of ‘axons’ to every other node
in the network. The massively parallel architec-
ture of these circuits was anticipated in Golgi’s
observation that areas of the brain might func-
tion simultaneously through their nervous net-
works.
Although the networks assume that the
weights of the connections represent synaptic
strengths, they could just as well represent the
strengths of continuous connections. Further-
more, in these networks with their ‘hidden
units’, the individuality of the individual nerve
cell is merged with the action of the network as
a whole. Thus, I do not think there is much
doubt that Golgi would view modern neural net-
works as precisely the kind of ‘nerve organ’ that
he proposed in which ‘every nerve element con-
tributes’, and that is necessary for the higher
cognitive functions of the brain. One of the chal-
lenges for modern computational neuroscience
is to put real properties of neurons, especially
their dendrites, into neural networks, so that
these networks will carry out ‘neural processing’
in ways that more closely reflect how the brain
actually does it (cf. Churchland & Sejnowski,
1987; Shepherd, 1990; Segev et al., 1995).
From Nutritive Dendrites to Neuroenergetics
The third idea of Golgi is his belief that the role
of the dendrite is primarily nutritive. This seems
to me to reflect his training as a physician and
neuropathologist, giving him a broad view that
recognized that, in addition to its ‘neural’ func-
213
tions underlying mental activities, the brain
would have to provide for the nutrition and me-
tabolism of its cells like any other organ of the
body. This required thinking about the relation
between nerve cells and their blood supply. At
that time, the clearest evidence of this was the
relation of dendrites in the grey matter to the
blood vessels of the pia.
Although here again the anatomical basis for
this relation has been transformed by modern
research, Golgi’s focus on these issues can be
regarded as one of the first steps toward under-
standing the metabolic basis of brain function. It
does not seem unreasonable to recognize that
modern brain imaging, based on PET or fMRI,
builds on this foundation. These issues may be
expected to receive increasing attention as we
move from generating low resolution brain
scans of different regions involved in particular
brain functions toward the emerging field of
‘neuroenergetics’, concerned with the cellular
basis of brain images (Yang et al., 1998). These
studies at the cellular level make clear the cru-
cial role of glia as intermediaries between neural
energy demands and changes in blood flow to
meet them (cf. Magistretti, 1996). I do not think
there is much doubt that Golgi would feel he had
a right to be considered a pioneer in raising
these questions as well.
The Golgi Apparatus: Connecting the Soma
with Synapses
Finally, we honor Golgi this year for his discov-
ery of the intracellular organelle bearing his
name. This organelle has become central to all
concepts of the secretory functions of cells in
general and nerve cells in particular. The fact
that the Golgi apparatus is so closely related to
functions of synapses, a concept of Cajal that
Golgi fought all his life, is another irony illus-
trating that experimental discoveries have lives
of their own. Cajal (1989) observed plaintively
that he seemed fated to be linked forever to
Golgi despite their opposing views on ‘Neuron-
ism’ and ‘Reticularism’. The Golgi apparatus is
an even more symbolic link, because it is
through the Golgi apparatus that transmitter sub-
stances are manufactured and packaged for ex-
port to the terminals, where they are secreted by
214 GORDON M. SHEPHERD
the synapses to link neurons into the functional
circuits in which Cajal so fervently believed.
SUMMARY
In summary, Golgi combined experimental inno-
vation with a conceptual holism. The experi-
mental methods provided the foundations for the
development of the cellular basis of modern
neuroscience and clinical neurology. The con-
cepts seemed to be disproved by those very
methods, but a closer examination reveals that
he may have been thinking in more abstract
functional frameworks about brain organization.
Those frameworks are the antecedents of mod-
ern concepts of brain organization and function
emerging currently from the methods of compu-
tational neuroscience and brain imaging.
ACKNOWLEDGMENTS
The author would like to thank P. Mazzarella and M.
Bentivoglio for valuable discussions. Our work has
been supported by grants from NIDCD and from
NIDCD, NASA and NIMH (Human Brain Project).
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