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18. Changeux, J. P. Cajal on neurons, molecules, and 23. Gallego, A. Reflejo de la obra de Cajal en la neurofisiologa Online links
consciousness. Ann. NY Acad. Sci. 929, 147151 moderna. An. Ins. Farm. Esp. 1112, 2550 (1963).
(2001). 24. Ramn y Cajal, S. Recuerdos de Mi Vida: Historia de Mi DATABASES
19. Sherrington, C. S. Double (antidromic) conduction in the Labor Cientfica 3rd edn (Juan Pueyo, Madrid, 1923). The following terms in this article are linked online to:
central nervous system. Proc. Roy. Soc. Lond. B 61, 25. Droz, B. in The Nervous System (ed. Tower, D. B.) OMIM:http://www.ncbi.nlm.nih.gov/Omim/
243246 (1897). 115127 (Raven, New York, 1975). Kallmann syndrome
20. Ramn y Cajal, S. Significacin probable de las clulas 26. Ramn y Cajal, S. Cajals Degeneration & Regeneration
de axon corto. Trab. Lab. Invest. Biol. Univ. Madrid 1, of the Nervous System (eds DeFelipe, J. & Jones, E. G) FURTHER INFORMATION
151157 (1901). (Oxford Univ. Press, New York, 1991). Encyclopedia of Life Sciences: http:www.els.net/
21. Piccolino, M. Cajal and the retina: a 100-year 27. Sotelo, C. & Alvarado-Mallart, R. M. The reconstruction of Ramn y Cajal, Santiago
retrospective. Trends Neurosci. 11, 521525 (1988). cerebellar circuits. Trends Neurosci. 14, 350355 (1991). MIT Encyclopedia of Cognitive Sciences:
22. Ramn y Cajal, S. Les problmes histophysiologiques de http:cognet.mit.edu/MITECS/
la rtine. XIV Concilium. Ophthalmologicum Hispaniae Acknowledgements Cajal, Santiago Ramn y | Golgi, Camillo
11, 1119 (1933). I thank J. Lerma and H. Korn for useful discussions. Access to this interactive links box is free online.
channels. This insight drove him to depict fibre, whereas the opposite effect was easily under certain conditions, accompanied by the
the direction of nervous currents in neu- observed. A final understanding of this fun- inhibition of segmental reflexes. Not being
ronal networks, with arrows in his drawings damental concept required the acceptance of aware of inhibition as a specialized neuronal
(FIG. 2a,b). The implication of his vision was chemical synaptic transmission and the function, he proposed that such inhibition
that he could tell the functional organization demonstration of the ultrastructural asym- was a form of saturation that would occur
of circuits by looking at the anatomical metry between the presynaptic and post- with very large incoming messages3. Our pre-
arrangements of the constituting network synaptic terminals13. Today, we know that some sent understanding of inhibition had to await
it was a bold step indeed. feedback modulation does exist and that a the demonstration of chemical synaptic
In a similar functional vein, he further certain degree of presynaptic self-modulation transmission by John Eccles (REF. 14).
proposed that this dynamic polarization was is present, but even the most recalcitrant One of the most exciting aspects of Ramn
the basis of the fundamentally unidirectional scientists among us know that neuronal y Cajals thinking emerged from his study of
nature of neuronal circuit organization, from networks cannot really run backwards. comparative neuroscience. He marvelled at
the sensory to the motor domains. Indeed, Concerning the functional organization of the issue of network size versus functional
Charles Bell had shown, in 1811, that the ven- neuronal networks, given their divergent complexity. In comparing the nervous system
tral spinal roots had an exclusively motor func- nature Ramn y Cajal proposed that the of a large vertebrate with that of invertebrates
tion8, whereas Francois Magendie, in 1822, anatomical organization favoured what he such as the squid or small insects, Ramn y
provided proof of the exclusively sensory termed avalanche conduction3, in which a Cajal was amazed that all three can solve
nature of the dorsal roots and the unidirec- small, well-defined stimulus could result in the equally complex problems such as eating,
tionality of dorsal to ventral root conduction activation of a large number of neurons. He swimming, flying, fighting and reproducing,
(REFS 9, 10; and see Fultons discussion in REF. 11). considered this to be important in light of our despite the extraordinary differences in brain
Ramn y Cajal stopped short of proposing ability to detect even the smallest of sensory size. Indeed, he compared the differences
that the unidirectionality of network conduc- stimuli, which would require the initial signal between large and small nervous systems to
tion was a fundamental property that was to be amplified to attain cognitive threshold. the contrast between large clocks such as Big
derived from the one-way conduction of The idea of inhibition as a neuronal prop- Ben and wristwatches15. Although the differ-
synapses. This crucial step was not finally erty was missing in Ramn y Cajals descrip- ences in size are enormous, both timepieces
taken until Hagiwara and Tasaki12 made tion of network function. But he was aware tell the time with similar accuracy.
simultaneous recordings from the presynaptic that inhibition existed and referred to it in his Concerning the retina (FIG. 3), Ramn y
and postsynaptic fibres at the squid giant writings3. Indeed, he was aware of the crossed Cajal wrote that the complexity of the
synapse and showed that postsynaptic spikes inhibitory reflex in the spinal cord and the fact insect retina is stupendous, indeed dis-
did not activate the adjoining presynaptic that cortical input to the spinal cord was, concerting, and with no precedent in other
Figure 3 | Physical dimensions of the neuronal circuits of a mammal, a cephalopod and an insect. In a the organization and size of the mammalian visual
system comprising the retina (19), optic nerve (NO) and the central nervous system (L) is more than one order of magnitude larger than that of a cephalopod
(Sepia) in b. The cephalopod system is more than one order of magnitude larger than that of a housefly in c. However, all three do a good job imaging and
detecting movement, given the requirements of each animal. Reproduced, with permission, from the Instituto de Neurobiologa Ramn y Cajal, Madrid, Spain.
animals indeed, the retina of vertebrates To many of us, Ramn y Cajal personifies, 6. Sotelo, C. Viewing the brain through the master hand of
Ramn y Cajal. Nature Rev. Neurosci. 4, 7177 (2003).
seems by contrast gross and deplorably sim- above all, the belief that we actually can under- 7. Ramn y Cajal, S. Estructura del kiasma ptico y teora
ple (REF. 15, pages 389390). We now stand the nervous system, which represents, general de los entrecruzamientos de las vas nerviosas.
Rev. Trim. Microgrfca 3 (1898)
know that this is not really the case, as the more than anything else, the very nature of 8. Bell, C. An Idea of a New Anatomy of the Brain;
complexity of the vertebrate retina easily what we are. The image that comes to mind Submitted for the Observations of his Friends (Strahan &
Preston, London, 1811).
rivals that of any other in the phylogenetic relates to the account by Wilder Penfield of his 9. Magendie, F. Expriences sur les fonctions des racines
scale. But if we compare the neuronal size visit to the old master shortly before his death, des nerfs rachidiens. J. Physiol. Exp. Pathol. 2, 276279
(1822).
and complexity of, say, the early stages of which appears as an appreciation of Ramn y 10. Magendie, F. Expriences sur les fonctions des racines
the visual system in mammals (FIG. 3a), Cajal in the English translation of his scientific des nerfs qui nascent de la molle pinire. J. Physiol.
Exp. Pathol. 2, 366371 (1822).
cephalopods (FIG. 3b) and insects (FIG. 3c) it is testament Neuron Theory or Reticular 11. Fulton, J. F. Physiology of the Nervous System (Oxford
clear that the most amazing miniaturization Theory? 17. Penfield describes him, relegated to Univ. Press, New York, 1938).
12. Hagiwara, S. & Tasaki, I. A study on the mechanism of
of network architecture is found in insects. his bed, drawing a pyramidal dendritic spine, impulse transmission across the giant synapse of the
squid. J. Physiol. (Lond.) 143, 114137 (1958).
Consider, for example, that the thinnest neu- nervously placing his quill into ink and, before 13. Couteaux, R. Motor endplate structure in Structure and
rites in the CNS of insects might be as thin as guiding it to the paper, shaking yet another Function of Muscle (Bourne, G.) 337 (Academic, New
York, 1960).
50 nm (REF. 16); that is, of the same order of drop on to the large ink stain on the wall to the 14. Eccles, J. C. The nature of central inhibition. Proc. R.
magnitude as a synaptic vesicle. The biophys- right side of his bed. Yet another drawing of Soc. Lond. B 153, 445476 (1961).
15. Ramn y Cajal, S. Recuerdos de Mi Vida: Historia de Mi
ical problems that are introduced by such a his beloved brain studies, the stated reason for Labor Cientfica 3rd edn (Juan Pueyo, Madrid, 1923).
degree of size optimization are worth serious his own existence. 16. Meinertzhagen, I. A. and ONeil, S. D. Synaptic
organization of columnar elements in the lamina of the
consideration. Issues such as the input resis- Rodolofo R. Llins is at the Department of wild type in Drosophila melanogaster. J. Comp. Neurol.
tance of a neuronal process with an internal Physiology and Neuroscience, New York University 305, 232263 (1991).
17. Ramn y Cajal, S. Neuron Theory or Reticular Theory?
diameter of 35 nm, or the integrative proper- Medical School, New York, New York 10016, USA. (Consejo Superior de Investigaciones Cientficas, Madrid,
ties of dendrites in neurons where the gating e-mail: llinar01@popmail.med.nyu.edu 1954).
of a single ion channel could drive trans- doi:10.1038/nrn1011
Acknowledgement
membrane voltages to amplitudes that rival I thank I. Meinertzhagen for conversations on neuronal size
1. Popper, K. Logik der Forschung (Springer, Vienna, 1934). in insects.
action potentials, are not every day fare. If we 2. Ramn y Cajal, S. The Croonian Lecture. La fine structure
consider insects such as the tiny Costa Rican des centres nerveux. Proc. Roy. Soc.Lond. B 55,
wasp Dicopomorpha echmepterygis, which 444468 (1894). Online Links
3. Ramn y Cajal, S. Textura del Sistema Nervioso del
has a total body length of 135 m and a head Hombre y de los Vertebrados (Moya, Madrid, 1899). FURTHER INFORMATION
diameter of 40 m, we can only wonder at 4. Ramn y Cajal, S. Leyes de la morfologa y dinamismo de
las clulas nerviosas. Rev. Trim. Microgrfca 2, 112
Encyclopedia of Life Sciences: http:www.els.net/
neural information processing | Ramn y Cajal, Santiago
the degree of miniaturization that is ulti- (1897). MIT Encyclopedia of Cognitive Sciences:
5. Ramn y Cajal, S. Sobre las fibras nerviosas de la capa http:cognet.mit.edu/MITECS/
mately achievable by biological neuronal molecular del cerebelo. Rev. Trim. Histol. Normal Patol. 1, Cajal, Santiago Ramn y | neural networks
networks. 3349 (1888). Access to this interactive links box is free online.