Sabtuagi Ramón y Cajal Shows How Neurons Work
Santiago Ramón y Cajal was a pivotal figure in the late nineteenth century who transformed our understanding of the nervous system. At that time, scientists were divided between the reticular theory, which posited that nerve fibers formed a continuous network, and Cajal's emerging neuron doctrine, which asserted that neurons are distinct, individual cells that communicate via contact rather than continuity. Utilizing innovative staining techniques and meticulous microscopy, Cajal identified unique structures within the nervous system, including basket cells and mossy fibers, and demonstrated that neurons transmit impulses in one direction. His findings laid the foundation for modern neuroscience, influencing various fields such as psychology, physiology, and medicine.
Cajal’s work not only provided insight into the structure of the brain but also offered a clearer understanding of cognitive functions, learning mechanisms, and neurological disorders. His contributions culminated in the first clear depiction of the synapse, which has critical implications for medical treatments and therapeutic approaches to nerve damage. For his groundbreaking discoveries, Ramón y Cajal was awarded the Nobel Prize in Physiology or Medicine in 1906, marking a significant recognition of his influence on science. Today, his legacy continues to shape our comprehension of neural function and the intricate workings of the brain.
Sabtuagi Ramón y Cajal Shows How Neurons Work
Date 1888-1906
Ramón y Cajal showed that nerve cells operate as the discrete entities that transmit impulses unidirectionally in the nervous system through specific points of contact. His neuron doctrine influenced histologists, physiologists, surgeons, pathologists, neurosurgeons, psychiatrists, psychologists, and educational theorists.
Locale Madrid, Spain
Key Figures
Santiago Ramón y Cajal (1852-1934), Spanish histologist, physician, and winner of the 1906 Nobel Prize in Physiology or MedicineCamillo Golgi (1843-1926), Italian anatomist and physicianRudolf Albert von Kölliker (1817-1905), Swiss embryologist and histologistPaul Ehrlich (1854-1915), German chemist
Summary of Event
During the late nineteenth century, a controversy existed among brain scientists as to the nature of impulse transmission through the nervous system. The more popular school of thought began in 1872, when the gray matter of the cerebrum (brain) was described as a diffuse nerve net with fusion of dendrites (fine processes). Such notables as Theodor Meynert and Camillo Golgi agreed with this “reticular theory.”
According to reticular theory, the proper impulses were directed somehow out from this network of fused fibers to the appropriate muscles and organs, much like the streams flowing out from a lake being directed to specific locations. A. H. Forel showed that retrograde degeneration was confined to the damaged cells, and Wilhelm His showed that in embryos the nerve cells behave as centers giving origin to fiber outgrowths. At the time, the physical evidence was inadequate for determining which theory was more correct. No one had been able to see, with any clarity, the nerve fiber endings. Yet, Santiago Ramón y Cajal was able to provide the irrefutable evidence that resolved the issue eventually.
Ramón y Cajal’s legacy was born of the microscope, an instrument he first became familiar with in 1877 while studying in Madrid. He soon became expert in histology, the field of biology devoted to the study of tissues. In the process, he made innovations in the staining techniques of the time. Tissue staining is a technique of applying dyes or other chemicals to the material studied so that particular structures or features are seen more easily.
While at the University of Barcelona in 1888, Ramón y Cajal made a major finding while working with bird and small mammal embryos. He studied those specimens because embryonic nerve cells have fewer interconnections and are not covered with myelin, a fatty layer of insulation that covers the axons, or long processes, of most adult neurons, allowing individual cells to stand out. He also modified the chrome silver staining technique invented by Golgi. Focusing on the cerebellum of the brain, Ramón y Cajal discovered basket cells and mossy fibers. He found that the long processes (axons) of the nerve cells terminate in proximity, not continuity, with other cells or dendrites. This suggested that the nervous system works by contact, and thus Ramón y Cajal developed his “law of transmission by contact.” For the first time, it was proposed that the cells were the important components of the nervous system, as opposed to the fibers, which previously were believed to be a continuous network that transmitted impulses in the system. The popular notion was that the cells played a relatively minor, supportive role. Ramón y Cajal’s evidence of definitely limited conduction paths in the gray matter would be substantiated by later investigations of the retina, spinal cord, and other brain regions. Yet, the reticular theory proponents would not be defeated so easily.
After giving a presentation to the German Anatomical Society in Berlin in 1889, Ramón y Cajal won the support of Rudolf Albert von Kölliker, then editor of a scientific journal. Kölliker helped to promote the theories of Ramón y Cajal throughout Europe.
In 1890, Ramón y Cajal turned to a different set of studies that would support his theory. He demonstrated that developing nerve cells send out axon “growth cones” that later sprout dendrites and make connections, supporting the theory of His and Kölliker. There was an alternate theory favored by the “reticular” advocates stating that developing nerves arise from the fusion of a row of cells.
In 1891, Ramón y Cajal returned to studying the cerebrum, a subject of some investigations several years past. He published a well-received book of his results. Wilhelm Waldeyer coined the term “neuron”; Ramón y Cajal’s ideas became known as the “neuron theory.” In 1892, Ramón y Cajal proposed his neurotropic theory to explain how the growth cone of the developing neuron is directed to its proper target. For the next few years, he would work on the retinas of various animals and on the hippocampus. The consistency of the results, with respect to his neuron theory, was unequivocal.
In 1896, Ramón y Cajal learned of Paul Ehrlich’s methylene blue technique for staining tissues. This was a nontoxic substance and thus could be applied to living animals. Ramón y Cajal repeated many of his findings on living specimens using this technique to refute the criticism from such reticularists as Golgi that his results were an anomaly of his previous methods on dead tissues. Again, the results were irrefutable: Nerve cells existed as distinct units, making only the barest contact with other nerve cells in the system. Detractors of the neuron theory persisted. They objected on the grounds that Ramón y Cajal had not shown that neuron fibrils (internal structures) were not continuous, as they had claimed in support of the reticular theory.
The beginning of the twentieth century found Ramón y Cajal in Paris to receive the Moscow Prize of the Thirteenth Medical Congress. Not only did he receive the prestigious award, with its monetary bonus, but also the congress awarded Madrid the venue for the next congress to be held in 1903. This brought great praise and adulation to him at home. He was appointed director of the new National Institute of Hygiene, where he promptly persuaded the authorities to establish a laboratory of biological research. The government finally was supporting science in Spain.
By 1903, Ramón y Cajal had perfected yet another staining technique—reduced silver nitrate —which made the tissue transparent, allowing him to discover details about the internal structures of the nerve cells, including fibrils. He published twenty-two papers that year on fibrillar discontinuity, consistent with his neuron doctrine. Dozens of other scientists confirmed his work. For all intents, the debate over reticular versus neuron was won, but some die-hard reticular advocates persisted, even into the 1950’s.
The recognition of Ramón y Cajal’s theories reached a pinnacle in 1906, when he was awarded the Nobel Prize in Physiology or Medicine. Somewhat ironically, he shared the prize with Golgi, whose staining technique had made many of Ramón y Cajal’s early findings possible, but who was still an advocate of the reticular hypothesis and a severe critic of Ramón y Cajal, so much so that he embarrassingly used his Nobel lecture to attempt a critique of Ramón y Cajal’s methods and results. History would forgive Golgi his myopia and would establish Ramón y Cajal as a scientist of tremendous impact on modern neuroscience.
Significance
The neuron doctrine of Santiago Ramón y Cajal had an impact on many different fields within biology and medicine. The knowledge of the actual functional structure of the brain—being made of discrete, contacting units that transmit impulses in one direction—gave a better physical basis for understanding many nervous or mental disorders. Treatment now could be approached with a more accurate perspective on the possible deficiencies in the disorders. A modern understanding of impulse transmission through the nervous system, from sensory neurons to central nervous system and then to muscle, is directly reflective of Ramón y Cajal’s theory. The “black box” that had existed between the reception of a stimulus event and the control of a motor response, while still not completely revealed, was at least partly illuminated by this work.
Possible mechanisms of learning and memory were developed with the framework established by the neuron doctrine. The foundation for the concept of the final common pathway of Sir Charles Scott Sherrington, the principle of reflex activity that is adhered to still, was laid by Ramón y Cajal and his microscope.
The concepts of neural inhibition, summation, and facilitation that are accepted now are possible only within the context of the neuron doctrine. English physiologists were led to their work on the synapse, the site of neuron-to-neuron communication, by Ramón y Cajal’s studies, and this knowledge of the synapse has had a great impact on medicine such as in drug therapy and in the treatment of neurological disorders.
Ivan Petrovich Pavlov’s famous treatise on conditioning was molded, at least in part, by the neuron doctrine, as was the work of Walter Bradford Cannon on the physiological aspects of emotion. Ramón y Cajal’s work could be said to have had an impact on education because his neuron doctrine has influenced subsequent theories on mechanisms for learning.
In the course of developing his neuron doctrine, Ramón y Cajal made a number of advances and innovations in histological staining techniques, many of which are still the techniques of choice. The work conducted on regeneration in the nervous system has played a seminal role in nerve damage therapy.
It is possible that had it not been Ramón y Cajal, someone else would eventually have discovered the truth about the structure of the nervous system and the nature of impulse transmission. Nevertheless, this man of meager means and modest beginnings had the inspiration and fortitude to pioneer the murky waters of the time, to bring science out of the ignorance of complacency. His work had a domino, rippling effect on the direction of science, such that the rate of progress in the field of neuroscience has been phenomenal. If Ramón y Cajal had not paved the way, scientists may have been stumbling along into untold dead-ends for many years.
Bibliography
Bullock, Theodore Holmes, Richard Orkand, and Alan Grinnell. Introduction to Nervous Systems. San Francisco, Calif.: W. H. Freeman, 1977. Although this book is written for college and medical students, portions of it are accessible to the general reader. In particular, the introduction gives a good overview of the field of neuroscience. Ramón y Cajal’s work is evidenced in nearly every chapter. A special section of chapter 3 gives a chronology of the debate over the structure of the brain. Includes illustrations, a glossary, a reference section, and an index.
Cannon, Dorothy F. Explorer of the Human Brain: The Life of Santiago Ramón y Cajal: 1852-1934. New York: Henry Schuman, 1949. This biography’s narrative often includes the history of Spain during the periods discussed, putting the reader in a better perspective to appreciate Ramón y Cajal’s life. Numerous references and footnotes introduce the reader to the many other scientists who influenced and were influenced by Ramón y Cajal. Includes a bibliography and an index.
Carola, Robert, John P. Harley, and Charles R. Noback. Human Anatomy and Physiology. 2d ed. New York: McGraw-Hill, 1992. An introductory college-level book. Includes many colorful diagrams and illustrations that will help the reader learn more about the structures and concepts of the nervous system and nerve cells. Full-color photomicrographs also are included. Includes an index, an extensive glossary, and appendices.
Fincher, Jack. The Brain: Mystery of Matter and Mind. Washington, D.C.: U.S. News Books, 1981. Written especially for the general public in a very nontechnical style. Includes several references to Ramón y Cajal and a brief description of the reticular versus neuron debate. Colorful illustrations and photographs, with a section in chapter 3 that covers the details about the neuron. Other chapters cover memory and learning, emotional aspects of the brain, language processing, and medical advances. Glossary and index.
Finger, Stanley. Minds Behind the Brain: A History of the Pioneers and Their Discoveries. New York: Oxford University Press, 2000. A collection exploring the history of neuroscience. Includes the chapter “Santiago Ramón y Cajal: From Nerve Nets to Neuron Doctrine.”
Ramón y Cajal, Santiago. Texture of the Nervous System of Man and the Vertebrates. Edited and translated by Pedro Pasik and Tauba Pasik. New York: Springer, 1999. An annotated translation of Ramón y Cajal’s 1899 work on the nervous system.
Williams, Harley. Don Quixote of the Microscope: An Interpretation of the Spanish Savant, Santiago Ramón y Cajal, 1852-1934. London: Jonathan Cape, 1954. A biography of Ramón y Cajal written in a very literary style, at times a bit overly dramatic and prosaic. Provides a different perspective. A brief reference list is included.