Key Thinkers in Neuroscience

Andy Wickens

• Publisher: Routledge
• Year: 2018
• ISBN:
  9781351271028
• Edition: 1
• Topic: Psychologie
• Subtopic: Histoire et théorie en psychologie

Key Thinkers in Neuroscience provides insight into the life and work of some of the most significant minds that have shaped the field. Studies of the human brain have been varied and complex, and the field is rich in pioneers whose endeavours have broken new ground in neuroscience.

Adopting a chronological and multi-disciplinary approach to each Key Thinker, the book highlights their extraordinary contributions to neuroscience. Beginning with Santiago Ramon y Cajal and finishing with the philosophers Patricia Churchland and Paul Churchland, this book provides a comprehensive look at the new ideas and discoveries that have shaped neuroscientific research and practice, and the people that have been invaluable to this field.

This book will be an indispensable companion for all students of neuroscience and the history of psychology, as well as anyone interested in how we have built our knowledge of the brain.

Chapter 1
Santiago Ramón y Cajal (1852–1934)

If there is one person above all others who is the father of modern neuroscience, then it is surely Santiago Ramón y Cajal, whose work led to the formulation of the neuron doctrine, which holds that nerve cells form the fundamental structural and functional units of the nervous system.

The early portends for the father of modern neuroscience were not promising. The son of a struggling country doctor, born in the small town of Petilla de Aragon in north eastern Spain, Cajal was a headstrong and rebellious youth, expelled from school and often punished for bad behaviour. This included an act of vandalism at the age of 11 when he blew a hole in his neighbour’s gate with home-made explosive! Although recalcitrant, Cajal had a passion for drawing and dreamed of becoming a painter, although he was first apprenticed as a shoe-maker and then a barber. Fortunately, his father managed to turn his wayward son’s interest to anatomy after teaching him about the human skeleton using bones that had allegedly been unearthed from a local cemetery. Cajal would later confess, “Henceforth, I saw in the cadaver, not death … but the marvellous workmanship of life”. This formative experience encouraged him to begin medical training at the nearby University of Zaragoza. After graduating in 1873, Cajal served in Cuba, and then under the Spanish rule, he served as a military doctor. However, he would spend less than 2 years in Cuba before contracting malaria and tuberculosis. In a state of frail health, Cajal went back to Spain intent on changing vocation.

In 1875, Cajal returned to the University of Zaragoza as assistant professor – a position enabling him to study for his doctorate. Two years later after passing his examinations in Madrid, Cajal spotted a modest microscope for sale in a shop, with a magnification sufficient for his research interests. Using every peseta he had saved from Cuba, Cajal purchased the instrument and took it home where he set up a laboratory to examine the pathogenesis of inflammation. At the time, Cajal was still in poor health and suffered a pulmonary haemorrhage in 1878. Nonetheless, his investigations, some of it examining how nerve fibres terminated in muscle, led him to be appointed as director of the anatomical museum at the University of Zaragoza in 1879. He then rose to chair of anatomy at the University of Valencia in 1883 – a period that also saw Cajal publishing his first scientific papers. Interestingly, while his full surname was Ramón y Cajal, he dropped the surname of his father (Ramón) and tended to publish his work simply as Cajal (the surname of his mother).

At the age of 35, in 1887, Cajal moved to the University of Barcelona. It proved to be a turning point in Cajal’s research life, for in the same year he was shown samples of nerve cells stained with the silver impregnation method. This technique invented by the Italian Camillo Golgi in 1873 was one that only stained a small percentage of neurons (around 2%) in any preparation of nervous material. But far from being a disadvantage, this allowed the few affected neurons to stand out in black against a silvery-yellow background. Now, the cell’s morphological features such as their dendrites could be viewed in unsurpassed clarity and axons followed through the nervous morass. Enthralled by what he saw, Cajal vowed to learn the technique, although his first attempts to do so were disappointing since the results were capricious and unreliable. But with a little experimentation, Cajal realised that if he stained the tissue twice, this markedly improved the reliability and effectiveness of the technique. And even better results were obtained if he stained unmyelinated axons – a finding that prompted him to use his technique on young animals.

At this point, Cajal engaged in a feverish burst of research – staining many areas of the brain and drawing his observations. Realising this work was providing many new findings, he began publishing his own journal, with copies sent to the most important neuroanatomists of Europe. The inaugural copy appeared in 1888, with six articles by Cajal, in a format that was to set new standards for reporting neuroanatomical findings. The first paper, for example, described the anatomy of the bird’s cerebellum. It showed the cerebellum to be a laminated structure with the axons of the small stellate cells in one layer ending freely over the cell bodies of the much larger Purkinje cells. Cajal also described the mossy fibres for the first time, which entered the cerebellum from an outside site and formed a relationship with the small dendrites of the granule cells. But Cajal’s real genius lay in the way he depicted these neuronal arrangements. From his drawings, the reader could see the neural structure of the cerebellum at a glance. In fact, his illustrations were a composite of many different drawings, based on numerous hours of meticulous microscopic examination and expressed with some degree of artistic imagination from Cajal’s own anatomical knowledge. Nonetheless, they captured the structural complexity of the cerebellum in exquisite detail. Even today, it can be argued that Cajal’s drawings of the nervous system have never been surpassed.

Cajal’s work, however, was to have a far bigger theoretical significance. For much of the nineteenth century, the prevailing view of the nervous system was that it formed a reticulum – namely, a continuous network of web-like interconnected or fused fibres. This theory had been developed by Joseph von Gerlach in 1872, although it was supported by Golgi, whose stain Cajal had enthusiastically adopted. But if this theory was correct, then it made the nervous system unique, for it was known all the other tissues of the body were made up of individual cells – a theory credited to Matthias Schleiden and Theodor Schwann in the 1830s. Nonetheless, right from the beginning of his research with the improved Golgi technique, Cajal was unable to find any evidence of axonal fusing, and it soon led him to assert with his characteristic forthrightness that nerve cells should be regarded like any other in the body – namely, independent units. Indeed, his observations showed that axons, instead of fusing, appeared to terminate as “free aborizations” on the dendrites of their recipient cells. It was an observation at odds with Golgi who had proposed that the dendrites only had a nutritive role in keeping the cell alive. A year later, Cajal came up with an even more profound idea when he deduced the direction of information flow through nerve cells. In short, he recognised that the dendrites provided the receptive part of the nerve cell, while the axon was its “emitting” and “distribution” apparatus. Cajal called his theory “the law of dynamic polarisation”.

Thus, Cajal had laid the foundations for a totally new understanding of the nervous system within a period of less than 2 years. Yet, despite his valiant attempts, Cajal’s work was not attracting attention from others – largely because Spanish was not widely read or spoken by the wider scientific community. In an attempt to address this, Cajal travelled to Berlin in 1889 to present his findings at an international congress. Unable to speak German and only managing a little broken French, Cajal set up his microscopes and invited delegates to view his silver-impregnated slides. One person to accept his invitation was Albert von Kölliker – then the most respected neuroanatomist of his time, who was also a champion of cellular theory and author of several hundred papers on tissue biology. Kölliker was immediately impressed with what he saw, and with his support Cajal was soon able to influence the rest of the neuroanatomy community with his pioneering research and ideas.

Around this time, other investigators were also beginning to cast a shadow on reticulum theory. One such researcher was the Swiss anatomist Wilhelm His. During the early 1880s, His had carefully followed the stages of early nervous system development in tissue taken from aborted human embryos aged between 2 and 8 weeks, and it led to the discovery that the spinal cord and its nerves arose from a primitive type of cell called a “neuropile”. But as he watched the axon fibre grow from the neuropile, followed by the emergence of the cell body and dendrites, at no point could he see the axons fuse as Golgi insisted. The same conclusion was also reached by another Swiss researcher, August Forel, who lesioned the motor cranial nerves in rodents and then traced the degeneration of the axons back to the brain. The results showed that the degenerating axons only produced small amounts of damage in small and specific areas of the brain stem. In other words, it was apparent that the axons were not continuous or joined with the neurons they reached in the brain – for if this was the case, then the degeneration should have been far more extensive and extend to many other areas. By 1891, the evidence had become so persuasive that Wilhelm Waldeyer was able to collect sufficient information to compile an extensive review supporting the concept of nerve cells, arguing they formed the main structural, embryological and functional units of the nervous system. In making his case, Waldeyer also referred to nerve cells as neurons. It was an inspired choice of term for the new theory would become known as the neuron doctrine – a phrase that helped encapsulate a biological principle supporting Cajal’s position.

Despite this, the neuron doctrine continued to be strongly criticised by the reticulists led by Golgi, who stuck to their belief that communication between axon fibres took place through continuity and not through direct contact. Indeed, the contact hypothesis was problematical for the neuron doctrine since it was not clear how the nerve impulse (which by now was known to be electrical in nature) could travel from one separate nerve cell to another. In this respect, the Golgi technique offered few clues. The strength of the Golgi stain had been its random selectivity. By only staining a small percentage of nerve cells in any tissue sample, it had made them highly visible for a microscopist to observe. But this was also a weakness when it came to establishing their connections since it was unlikely the stain would highlight two connecting nerve cells. And even if this did occur, the tiny cells of the nervous system meant that visualisation of the contact was beyond the resolution of the microscope of the times. The one exception to this was the much larger neuromuscular junction. Here, the motor fibre and muscle end plate could be seen in greater detail, and in 1886, the German Wilhelm Kühne reported that he could see a clear gap between the two. Kühne conveyed this to the Royal Society of London in 1888, speculating the nerve ending was open in some way, allowing its fluid to escape and cross the tiny gap, before reaching the muscle.

In 1894, Cajal received an invitation from the Royal Society to deliver their annual Croonian lecture. The decision to invite Cajal had come from Charles Sherrington whose main interest concerned the spinal circuitry of reflex action – work that required him to map the pathways of nerves from sensory stimulus to motor response. His attempts to trace the flow of information through the spinal cord had also convinced him that the nervous system was composed of nerve cells whose fibres made contact without fusing. Cajal travelled to London, gave his talk in French and stayed with the Sherrington family for his visit. It is not known if the two men discussed naming the contact point. However, soon after, Sherrington was invited to write a chapter in Sir Michael Foster’s Textbook of Physiology. He accepted, and in doing so he coined the term synapsis (from the Greek meaning “to clasp”) to describe the “surface of separation” between axon and nerve cell. The word soon morphed into synapse. Sherrington could only speculate how neural information might cross this junction. Nonetheless, he was certain that synapses existed – not least because he knew that the sum speed of reflex activity was much slower than the speed of nervous conduction.

In 1906, Golgi and Cajal were awarded the Nobel Prize in recognition of their work on elucidating the structure of the nervous system. It was also to be the only time the two men met. Sadly, they did not get on. Nor was the situation helped when Golgi in his acceptance speech strongly denounced Cajal’s nerve cell theory by telling the audience “it was going out of favour”. History has since shown that Cajal was correct in regard to the neuron doctrine and many other aspects of nerve function. In Golgi’s defence, it can be said that Cajal’s position was not proven in 1906, and for many the concept of a synapse was an implausible concept, leaving important questions about the nature of neural transmission unanswered. In fact, the existence of synapses in the central nervous system (CNS) would not be fully accepted until the invention of the electron microscope in the 1950s. Even then, there were those who opposed the idea of chemical neurotransmission.

If these were Cajal’s only achievements, they alone would have placed him in the pantheon of the greatest neuroscientists of all time. But there was much more which this short biography can only touch upon. In the years after he exploited the Golgi stain to describe the structure and function of the nervous system, thereby laying down the modern foundations of neuroscience, Cajal began working on the degeneration and regeneration of nerve fibres in the spinal cord and visual system. During this time, he also wrote several books of great importance, including his magnificent two-volume Textura del Sistema Nerviosa del Hombre y de los Vertebrados (Histology of the Nervous System of Man and Vertebrates) in 1904, which contained nearly 2000 pages and 887 illustrations – graphically revealing nearly every region of the brain. Over his long research career, Cajal would write almost 300 articles, found two scientific journals, help pioneer colour photography and serve as a director of several institutions. He also had time to write non-scientific books including Advice for a Young Investigator (1916) and a colourful biography Recollections of my Life (1917). Towards the end of his life, Cajal’s fame was so great that the Spanish authorities tried to put his portrait on bank notes and postage stamps (an accolade he refused to permit), although he accepted a life senator’s role in Madrid. Retiring from university work in 1922, Cajal continued writing until his death at the age of 83 in 1934. An obituary by the Italian neurologist Ernesto Lugaro eulogised that Cajal had contributed more to the knowledge of neuroscience than all the efforts of his fellow colleagues put together. Few would disagree.

Cajal’s major writings

Cajal, S.R. (1899/1904) Histology of the Nervous System of Man and Vertebrates. Translated by N.Swanson and L.W.Swanson. New York: Oxford University Press (1995).

Cajal, S.R. (1906) The structure and connexions of neurons. In: Nobel Lectures, Physiology and Medicine 1901–1921. New York: Elsevier (1967).

Cajal, S.R. (1913/1914) Degeneration and Regeneration of the Nervous System. Translated by R.M.May. London: Oxford University Press (1928).

Cajal, S.R. (1916) Advice for a Young Investigator. Translated by N.Swanson and L.W.Swanson. Cambridge, MA: MIT Press (1999).

Cajal, S.R. (1917) Recollections of my Life. Translated by E.H.Craigie, with the assistance of J.Cano. Cambridge, MA: MIT Press (1989).

Cajal, S.R. (1933) Neuron Theory or Reticular Theory? Objective Evidence of the Anatomical Unity of Nerve Cells. Translated by M.Ubeda-Purkiss and C.A.Fox. Madrid: Instituto Ramón y Cajal (1954).

Further reading

De Carlos, J.A. and Borrell, J. (2007) A historical reflection of the contributions of Cajal and Golgi to the foundations of neuroscience. Brain Research Reviews, 55, 8–16.

DeFelipe, J. (2002) Sesquicentennial of the birthday of Santiago Ramón Cajal (1852–2002), the father of modern neuroscience. Trends in Neuroscience, 25, 481–484.

DeFelipe, J. (2013) Cajal and the discovery of a new artistic world: The neuronal forest. Progress in Brain Research, 203, 201–220.

Jones, E.G. (1994) The neuron doctrine. Journal of the History of Neurosciences, 3, 3–20.

López-Muñoz, F., Boya, J. and Alamo, C. (2006) Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel Prize award to Santiago Ramón y Cajal. Brain Research Bulletin, 70, 391–405.

Shepherd, G.M. (1991) Foundations of the Neuron Doctrine. New York: Oxford University Press.

Sotelo, C. (2003) Viewing the brain through the master hand of Ramón y Cajal. Nature Reviews Neuroscience, 4, 71–77.

Swanson, L.W., Newman, E., Araque, A. and Dubinsky, J. (2017) The Beautiful Brain: The Drawings of Santiago Ramón y Cajal. New York: Abrams Books.

Chapter 2
Charles Scott Sherrington (1857–1952)

Sherrington’s greatest legacy to neuroscience was his eluci...

Table of contents

• Cover
• Half Title
• Title
• Copyright
• Contents
• Preface
• Acknowledgements
• Dedication
• 1 Santiago Ramón y Cajal (1852–1934)
• 2 Charles Scott Sherrington (1857–1952)
• 3 John Newport Langley (1852–1925)
• 4 Korbinian Brodmann (1868–1918)
• 5 Wilder Graves Penfield (1891–1976)
• 6 Edgar Douglas Adrian (1889–1977)
• 7 Henry Hallet Dale (1875–1968)
• 8 Walter Rudolf Hess (1881–1973)
• 9 Karl Spencer Lashley (1890–1958)
• 10 Giuseppi Moruzzi (1910–1986) and Horace Winchell Magoun (1907–1991)
• 11 Donald Olding Hebb (1904–1985)
• 12 Nathaniel Kleitman (1895–1999)
• 13 Andrew Lloyd Hodgkin (1914–1998) and Andrew Fielding Huxley (1917–2012)
• 14 Paul Donald MacLean (1913–2007)
• 15 John Carew Eccles (1903–1997)
• 16 Bernard Katz (1911–2003)
• 17 Seymour Solomon Kety (1915–2000)
• 18 Brenda Milner (b. 1918)
• 19 James Olds (1922–1976)
• 20 Julius Axelrod (1912–2004)
• 21 Rita Levi-Montalcini (1909–2012)
• 22 Roger Wolcott Sperry (1913–1994)
• 23 David Hunter Hubel (1926–2013) and Torsten Nils Wiesel (b. 1924)
• 24 Arvid Carlsson (1923–2018)
• 25 Norman Geschwind (1926–1984)
• 26 Paul Greengard (b. 1925)
• 27 Benjamin Libet (1916–2007)
• 28 Eric Kandel (b. 1929)
• 29 Bert Sakmann (b. 1942) and Erwin Neher (b. 1944)
• 30 David Coutnay Marr (1945–1980)
• 31 Mortimer Mishkin (b. 1926) and Leslie Ungerleider (b. 1946)
• 32 Timothy Bliss (b. 1940) and Terje Lømo (b. 1935)
• 33 Richard Axel (b. 1946) and Linda Buck (b. 1947)
• 34 Giacomo Rizzolatti (b. 1937)
• 35 John O’Keefe (b. 1939)
• 36 Michael Gazzaniga (b. 1939)
• 37 Joseph LeDoux (b. 1949)
• 38 Patricia Churchland (b. 1943) and Paul Churchland (b. 1942)
• Author index
• Subject index