Elucidating the Structure and Workings of the Nervous System

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Elucidating the Structure and Workings of the Nervous System

Overview

The detailed study of the nervous system did not begin in earnest until the middle of the nineteenth century. As with other areas of science, it was not until innovative technology was able to keep up with the new ideas that the structure and workings of the nervous system began to be discovered. Prior to the important discoveries of Camillo Golgi (1843-1926) in 1873 and Santiago Ramón y Cajal (1852-1934) in 1889, very little was known about the nervous system. This was especially true with regard to the microscopic structure of how each nerve cell was connected to the next one. This lack of understanding was due, in part, to the lack of appropriate staining techniques to help visualize a nerve cell (neuron) in the microscope.

In 1873 Camillo Golgi invented a technique for staining neurons that made it possible to observe and distinguish the three principle parts of the cell—the cell body, dendrites, and axon—with a microscope. This technique was termed the "black reaction" (reazione nera), based on a process that first hardened the nervous tissue and later impregnated it with a metallic stain. The revolutionary process that Golgi developed, which for the first time allowed a clear visualization of an entire neuron, is still used with minor modifications today. This advancement allowed other researchers to begin to study the intricacies of the nervous system in much more detail than was previously possible. This important contribution helped to set the stage for acceleration in the advancement of our knowledge in the area of the nervous system.

Golgi's research did not provide the answer to every question, however, and controversy ensued over the components of the nervous system. Although the theory that tissues were made up of individual cells had been put forth decades earlier, there was much debate regarding whether this theory should be applied to the nervous system. Golgi did not believe that the nervous system was made up of individual cells. Based on his own observations, Golgi believed in the "reticular theory" for the nervous system. This theory postulated that the nervous system was an intricate network of interconnected fibers and that the nerve impulses propagated along this diffuse network. At the same time, Wilhelm Waldeyer put forth the "neuron theory" for the nervous system. He believed that the nervous system was actually made up of individual cells that were functionally and anatomically different. The main supporter of this theory was Santiago Ramón y Cajal, who used the staining technique of Golgi to visualize the components of the nervous system. It is interesting to note that despite these fundamental philosophical issues, Golgi and Ramón y Cajal were both awarded the Nobel Prize for physiology or medicine in 1906 for their work elucidating the structure of the nervous system.

The most important investigation that helped to clarify the issue regarding the components of the nervous system was an observation made in 1889 by Ramón y Cajal. He believed that his slides of the nervous system clearly demonstrated that it was composed of individual units (neurons) that were structurally independent of one another and whose internal contents did not come into direct contact (synapses). According to this hypothesis, which now serves as the central idea in modern nervous system theory, each nerve cell communicates with others through contiguity rather than continuity. That is, communication between adjacent but individual cells must take place across the space that separates them. The idea that communication in the nervous system is largely between independent nerve cells served to be the guiding principle for further study in the first half of the next century.

Background

While the exact mechanisms for nerve transmission were not worked until after the mid-twentieth century, substantial progress to that goal was made in the first half of the century. There were many important discoveries in that time period. In 1932 Sir Charles Scott Sherrington (1857-1952) and Lord Edgar Douglas Adrian (1889-1977) were awarded the Nobel Prize for physiology or medicine for their research into the functions of neurons. However, much of this work was performed as much as three decades earlier. They made major contributions to our knowledge of the function of neurons regarding reflexes, and they pioneered a technique called electrophysiology that directly recorded the electrical activity of neurons.

Sherrington studied reflexes in experimental mammals and concluded that a reflex must be regarded as an integrated activity of the total organism. His initial line of evidence supporting what came to be known as "total integration" was his demonstration of the concept of reciprocal innervation of muscle. This stated that when one set of muscles is stimulated, the muscles opposing that action are simultaneously inhibited. He expanded further on reflexes in 1906 when he distinguished between three types of sensory receptors. One type he called proprioceptors, which he found were important structures in maintaining the postural reflex, a reflex that allowed animals to stand upright against gravity. He noted that this reflex occurred even if part of the brain was removed and tactile nerves were severed, so it must be governed by receptors found in muscles and joints.

Another important area of research during this time was the chemical transmission of nerve impulses, which culminated in the Nobel Prize for physiology or medicine for Sir Henry Dale (1875-1968) and Otto Loewi (1873-1961) in 1936. They provided the seminal work that demonstrated that transmission of nerve impulses involved the release of chemicals (neurotransmitters) from the nerve endings. The majority of their research was performed on the autonomic nervous system, but later these principles were extended to the entire nervous system.

Loewi provided the initial evidence that chemicals were involved in the transmission of impulses from one nerve cell to another or to an end organ. Their classical experiment involved stimulating the nerves, which slowed the heart of a frog, and then perfusing a second frog heart with fluids from the first frog heart. When the second heart also slowed, it indicated the presence of an active substance, which was produced by the initial nerve stimulation of the first heart. This substance was shown to be the neurotransmitter acetylcholine by Dale in 1929.

A significant development regarding the functioning of the nervous system came in 1929 when German psychiatrist Hans Berger (1873-1941) revealed his technique for recording electric currents generated in the brain by placing electrodes on the exterior of the skull, a technique called the electroencephalogram (EEG). Further studies demonstrated that this activity changed according to the functional status of the brain, such as in sleep, and in certain nervous diseases, such as in epilepsy. Hans Berger had succeeded in founding an entirely new branch of medical science, called clinical neurophysiology, which would have tremendous impact on the diagnosis and treatment of neurological diseases.

The individual properties of nerve fibers were also an area of intense interest. In 1944 Joseph Erlanger (1874-1965) and Herbert Spencer Gasser (1883-1963) received the Nobel Prize in physiology or medicine "for their discoveries relating to the highly differentiated functions of single nerve fibers." Their exhaustive experiments demonstrated that peripheral nerves vary according to their physical and conductive properties, as well as their function. They categorized nerves into three main groups (A, B, and C) according to their conduction velocities, degree of myelination, and diameters. Increased diameter and the greater degree of myelination resulted in faster conduction of nerve impulses. In addition, it was further discovered that the type of information conveyed along the nerve fiber was dependent upon the size. For instance, fibers relaying pain signals to the brain tended to be smaller, slow-conducting fibers, while fibers going to muscles tended to be larger, fast-conducting fibers.

Impact

The work done in the area of the structure and workings of the nervous system during the first half of the twentieth century had an important impact on society from both a scientific and medical view. Important discoveries took place that helped to advance our knowledge in this field of study, and many had important clinical applications. Most disorders are at least partially mediated by the nervous system, so it is absolutely essential that we have an excellent understanding of its inner workings. Besides the important scientific discoveries previously discussed, there were numerous other studies that helped to lay the foundation for future researchers to be successful.

The histological work done by Golgi and Ramón y Cajal helped to provide vivid representations of the nervous system on the cellular level. This research was important in that it gave scientists a picture of the intricacies of the nervous system. It also provided a tool that served to be useful in elucidating structures at the cellular level for other systems as well. Sherrington and his colleagues contributed to the knowledge base in nearly every aspect of nervous function and directly influenced the development of brain surgery and the treatment of such nervous disorders as paralysis and atrophy. In addition, Sherrington came up with much of the terminology regarding the nervous system that is still used today. For example, he denoted the terms neuron for a nerve cell and synapse for the point where an axon of a neuron meets either another neuron or some other end organ. Lastly, Sherrington, along with Adrian, pioneered the branch of science called electrophysiology, which directly records the electrical activity of neurons. This development was crucial in the eventual elucidation of how nerves transmit impulses.

For their part, Loewi and Dale provided extensive information regarding the nature of neurotransmitters. This information has subsequently been used to help understand the nature of certain toxins and to develop drugs to enhance or block the activity of neurotransmitters. And Hans Berger succeeded in founding an entirely new branch of medical science with the use of his EEG, called clinical neurophysiology. This instrument had tremendous impact on the diagnosis and treatment of many neurological diseases and is an important diagnostic tool in modern medicine. Finally, the information provided on the conduction velocities and properties of nerve axons by Erlanger and Gasser proved to be invaluable in understanding the nervous system. It had direct application to many disease processes. It was through these and other discoveries that modern medicine has advanced as quickly as it has.

JAMES J. HOFFMANN