Abstract and Keywords
This introductory chapter begins with a brief discussion of the many contributions of Santiago Ramón y Cajal, who is considered the father of modern neuroscience. He published almost 300 articles and several books of great importance, such as the classics Textura del Sistema Nervioso del Hombre y de los Vertebrados (1899-1904) and Estudios Sobre la Degeneración y Regeneración del Sistema Nervioso (1913-1914). He also received numerous awards and distinctions, including some of the most prestigious awards of his time: the Moscow Award (1900); the Helmholtz Gold Medal (1905); and the Nobel Prize for Physiology or Medicine (1906). The chapter then goes on to discuss why scientists often referred to trees and forests in their descriptions of the brain and, in particular, of the cerebral cortex, and how these neuronal forests served as an unlimited source of artistic and poetic inspiration to many scientists.
Santiago Ramón y Cajal (1852–1934) is considered the father of modern neuroscience for providing the first detailed analysis of the nervous system (DeFelipe, 2002a; Fig. F-1). Thus, we have honored his name in the title of this book, even though the figures contained in the main body of the text were composed by 95 different authors.
Cajal's studies and theories had a profound impact on the researchers of his era. He published almost 300 articles and several books of great importance, such as the classics Textura del Sistema Nervioso del Hombre y de los Vertebrados (Ramón y Cajal, 1899–1904) and Estudios Sobre la Degeneración y Regeneración del Sistema Nervioso (Ramón y Cajal, 1913–1914). He also received numerous awards and distinctions (Fig. F-1 right and F-2, left), including some of the most prestigious awards of his time: the Moscow Award (1900); the Helmholtz Gold Medal (1905); and the Nobel Prize for Physiology or Medicine (1906), which he shared with Camillo Golgi (1843–1926), the renowned Italian scientist who discovered the reazione nera (see “The Discovery of the Reazione Nera” in Section 2) and the organelle he defined as the “internal reticular apparatus” that was later called the Golgi apparatus (Bentivoglio, 1999). Over the years, Cajal has also received many tributes, such as the homage during the NASA Neurolab space flight mission in 1998 (Fig. F-2, right). The inclusion of “butterflies of the soul” in the title of this book refers to one of Cajal's favorite topics: the human neocortex and the most common neuron in the cerebral cortex, the pyramidal cell that he sometimes poetically named butterflies of the soul. In his book Recuerdos de Mi Vida, he wrote the following paragraph when he started studying the cerebral cortex:
I felt at that time the most lively curiosity—somehow romantic—for the enigmatic organization of the organ of the soul. Humans—I said to myself—reign over Nature through the architectural perfection of their brains [ … ]. To know the brain—we said to ourselves in our idealistic enthusiasm—is equivalent to discovering the material course of thought and will. [ … ] Like the entomologist hunting for brightly coloured butterflies, my attention was drawn to the flower garden of the grey matter, which contained cells with delicate and elegant forms, the mysterious butterflies of the soul, the beating of whose wings may some day (who knows?) clarify the secret of mental life. [ … ] Even from the aesthetic point of view, the nervous tissue contains the most charming attractions. In our parks are there any trees more elegant and luxurious than the Purkinje cells from the cerebellum or the psychic cell that is the famous cerebral pyramid?
Ramón y Cajal, 1917
The nervous system is made up of two main classes of specialized cells: neurons and neuroglia (or simply glial cells as I shall refer to them in the remaining text). The function of the brain, and of the nervous system in general, depends on the connections between neurons that are established through complex and specialized structures named synapses. These connections are organized into intricate networks or neuronal circuits, and they utilize electrochemical signals and neurotransmitters that are packed into small vesicles (synaptic vesicles) located in the presynaptic side of the synapse. In addition, close anatomical and functional coupling exists between neurons, glia, and blood vessels (see section, “The Beauty of the Nervous System: Neurons and Glia”).
As the reader will see, neurons and glia are arranged so that they constitute a true forest. Indeed, some types of neurons, like the pyramidal cells of the cerebral cortex (Fig. F-5a) and the Purkinje cells of the cerebellar cortex (Fig. F-5b)—the most (p.5)
This is why Cajal and other scientists often referred to trees and forests in their descriptions of the brain and, in particular, of the cerebral cortex. Another beautiful example is the following comment from Cajal regarding cortical plasticity:
These neuronal forests have served as an unlimited source of artistic and poetic inspiration to many scientists. Indeed, Figure F-6 is an artistic illustration showing a mysterious object, the brain, arising through the mist and emerging from the entangled branches of the trees that are condensed into an enchanted neuronal forest.
The cerebral cortex is similar to a garden filled with innumerable trees, the pyramidal cells, which can multiply their branches thanks to intelligent cultivation, send their roots deeper and producing more exquisite flowers and fruits every day.
Ramón y Cajal, 1894
Pío del Río-Hortega (1882–1945; Fig. F-7), one of Cajal's outstanding disciples, wrote the following marvelous paragraph describing the relationships between neurons, glia, and blood vessels:
In the landscape of the brain there are endless irrigation canals—blood vessels— and on their banks the bush-like cells—glia—collaborate in nerve function.
Del Río-Hortega, 1933
It is interesting to note that trees have also served as artistic symbols to describe biblical texts, which on occasion mention cognitive alterations. In Figure F-8, King Nebuchadnezzar II of Babylon (sixth century BC) is shown with dementia and eating grass “like the beasts in the field”; his walking “on all fours” refers to the extreme bending of his trunk (camptocormia) due to his parkinsonism associated with Lewy body disease. As a main theme in the illustration, a tree is shown whose trunk represents the kingdom with its inhabitants, the birds in their branches (Martín-Araguz, 2006). Here, we can also imagine a charming bridge between literature, artistic drawings, and neuroscience (compare Figs. F-5b and F-8).
Another artistic example of these early scientists is again from Cajal himself. Indeed, he was a master of bringing together science and art not only through his drawings but also through his photography. In fact, he was a pioneer in the development of color photography (Ramón y Cajal, 1912; Fig. F-9).
Cajal also inspired poets like Juan Ramón Jiménez (1881–1958; Nobel Prize for Literature in 1956; Fig. F-11), who in his book Españoles de Tres Mundos wrote:
In line with this poetic prose is the picture taken by Cajal himself in 1915 showing some trams in the Puerta del Sol, Madrid (Fig. F-11, right).
I saw him once in a tram, a long afternoon that rained full and blind, putting on his reading glasses through his silver hair, forgotten, leaning against the glass window, and that was how he remained, staring leisurely, abandoned and melancholic, into the horizon.
THE BEAUTY OF THE NERVOUS SYSTEM: NEURONS AND GLIA
In the nervous system there are billions of neurons and even more glia (at least 10 times more). As the reader will see under the section “A Sketch History of the Microscopic Anatomy of the Nervous System,” the discovery of the neuron has a long, fascinating history in which many researchers have participated up to the present day. Of course, glial cells are fundamental elements of the nervous system, and the history of these cells is tightly linked to that of the neuron. However, in the present book we shall only deal with these cells in a superficial manner. In general, neurons consist of (p.9)
As for axons, they adopt one of two general designs: (1) axons that only branch near the cell body from which they originate, such that neurons with this kind of axon are named interneurons or short-axon cells (Fig. F-12, right); (2) axons that leave the region where the cell body of origin is located, and these cells are known as projection neurons (Fig. F-12, left). In this case, the axon can travel over enormous lengths, which can often be in the order of several millimeters or even meters (for example, pyramidal cells projecting to the spinal cord in large mammals like the giraffe). Furthermore, the axon of projection neurons frequently gives rise to collaterals along its trajectory and, in turn, these collaterals can give rise to local axonal arbors that may be located near to or a distance from the cell body of origin (Fig. F-12, left). As an example of the richness of dendritic and axonal arborization and of the complexity of the organization of the nervous system, it has been estimated that there are approximately 3 km and 400 m of axonal and dendritic length, respectively, and an average density of 90,000 neurons per mm3 in the mouse cerebral cortex (Schüz and Palm, 1989). Furthermore, the brain is one of the organs of the body with the highest metabolic demands, and thus, there is a very dense network of blood vessels in association with the neurons and glia.
The exchange of information between neurons mainly takes place through two types of highly specialized structures: chemical synapses (the majority) and electrical synapses. The space between the cell bodies of the neurons, glia, and blood vessels—the neuropil—is occupied by a very dense network of axonal, dendritic, and glial processes. In the neuropil there is a high density of synapses, and, for example, there are approximately 1000 × 106 synapses per mm3 of neuropil in the human temporal cortex. Indeed, the neuropil represents between 90% and 98% of the volume of the cerebral cortex (Alonso-Nanclares et al., 2008). Thus, the main problem when analyzing the (p.10)
Thus, throughout the history of neuroscience, scientists have sought to develop appropriate methods to analyze different aspects of the structure and function of the nervous system. Some of these methods were discovered at random, whereas others were designed to resolve a given problem. Nevertheless, the development of science not only depends on the methods available but also on the ways they are exploited. Thus, there are examples of methods that were available to scientists but that were not fully exploited until an individual made an important discovery or an astute interpretation that generated new concepts. This was the case of the Golgi method, which remained unexploited for many years before Cajal entered the scene to change the course of the history of neuroscience (DeFelipe, 2002a, 2006; Jones, 2006; also see heading under Section 2 in this volume, “Cajal's First Study with the Golgi Method: Dendrites and Axons End Freely”).
A NOTE ON THE ILLUSTRATIONS
At the beginning of the nineteenth century and for several decades afterward, microphotography was not a well-established technique to study histology. Certainly, several types of microphotography accessories were available for light microscopy at that time, some of which were very sophisticated (Fig. F-15), but good techniques of microphotography had not yet been developed. Thus, obtaining high-quality microscopy images, particularly high-power microphotographs, was a difficult task. Moreover, the structure of the nervous system is very complex and the selective staining methods used, such as the Golgi method, do not define all (p.11)
Readers interested in the various methods to reproduce microscopy images and the material used to produce these drawings can consult the work of Cajal itself. His book entitled Manual de Histología Normal y de Técnica Micrográfica (Handbook of Normal Histology and Micrography Techniques) is of particular interest, which was first published in 1889 (Ramón y Cajal, 1889a) and then re-edited over the years with additional and corrected content (e.g., Ramón y Cajal, 1893, 1914). An English version of this work was published with the help of his disciple Jorge Francisco Tello (1880–1958), considered to be Cajal's first disciple (Ramón y Cajal and Tello, 1933; see DeFelipe and Jones, 1992). In general, the (p.13)
However, I would caution the reader that the use of the camera lucida does not mean that the drawing was always an accurate observation, since it depended on the interpretation of the observer. Indeed, the scientist's drawings of the histological preparations only illustrated those elements thought to be important for what they wanted to describe. As such, these illustrations were not necessarily free of technical errors. Finally, unless otherwise specified, most of the images in the present work are digitalized reproductions from the figures that appear in the publications or, in some cases, of the original drawings. Many of these figures have been retouched and restored in order to remove stains, wrinkles, or other artifacts (Fig. F-17) using Adobe Photoshop CS3 software (Adobe Systems Inc., San Jose, CA).