The Neuron Doctrine (1860-1895)

The neuron doctrine is a concept formed during the turn of the twentieth century that describes the properties of neurons, the specialized cells that compose the nervous system. The neuron doctrine was one of two major theories on the composition of the nervous system at the time. Advocates of the neuron doctrine claimed that the nervous system was composed of discrete cellular units. Proponents of the alternative reticular theory, on the other hand, argued that the entire nervous system was a continuous network of cells, without gaps or synapses between the cells. In 1873, physician and reticular theory supporter Camillo Golgi developed a staining technique called the black reaction, a neuron staining technique that allowed for complete visibility of nerve cells, which enabled scientists to view a complete neuron cell and its cellular structures. Later, neuroscientist Santiago Ramón y Cajal used the black reaction to show the existence of synapses, or gaps between neurons, and argued that his evidence supported the neuron doctrine. The confirmation of the neuron doctrine showed that neurons function as discrete and independent cells, not as a single network, within the nervous system.

During the late nineteenth century, scientists developed a theory called the neuron doctrine, which eventually established nerve cell characteristics, similar to the cell characteristics detailed in the cell theory. The cell theory states that cells are fundamental discrete units of life. Botanist Matthias Jakob Schleiden and zoologist Theodor Schwann in the mid nineteenth century in Germany described the cell theory that developed into the following three general characteristics: a cell is the most basic unit of life, all living organisms are composed of one or more cells, and all cells arise from living cells.

However, applying the cell theory to nerve cells proved complicated. Nervous tissue is structurally different from all other tissues due to the branching shape of neurons. Scientists had a difficult time differentiating one neuron from another because their cellular extremities, later called axons and dendrites, appeared as one unit. Axons are the thin singular cell extremities that carry nerve impulses through a nerve cell, whereas dendrites are the numerous branchlike extremities that receive those nerve impulses from surrounding cells.

The structural complexity and ambiguity of nervous tissue prevented scientists from physically studying neurons under a microscope until Golgi developed the black reaction. Prior to the black reaction, when scientists observed neurons they saw the cell body containing the nucleus, later called the soma, but could not fully distinguish the neurons' cellular extremities, later called dendrites and axon. At the time, scientists were unsure of the function and purpose of those cellular extremities. The inability to distinguish fully the structure of neurons prevented scientists from applying the perspectives of cell theory to study neurons as it was unclear whether the neurons functioned dependently or independently of one another.

Prior to the development of the black reaction, the staining techniques that scientists used to stain and study neurons under a microscope did not allow for the complete viewing of a neuron. In 1863 in Bonn, Germany, neuroscientist Otto Friedrich Karl Deiters used a neuron staining technique that involved the staining, hardening, and dissection under the microscope of a neural tissue sample. Deiters stained nerve tissue using a dye, often carmine, to add color and increase visibility of the neurons. After coloring the tissue, Deiters immersed the nerve tissue sample in a potassium dichromate solution, which hardened the delicate tissue and decreased the amount of damage done to the tissue when analyzing it. However, Deiters's method involved separating individual neurons with a needle under a microscope, which would often result in the tearing of cellular extremities.

Deiters recorded his findings as detailed drawings of neurons, but before he could publish his illustrations, he died of typhus on 5 December 1863. Dieter's depictions of neurons included the cell body holding the nucleus called soma, cellular branchlike extremities called dendrites, and nerve prolongations called axons. Deiters was unable to see the axon completely because the axons broke while he was studying nerve cells under a microscope due to their fragility. Because he was unable to completely view neurons, Dieter's illustrations did not show the ends of the axons and dendrites. After Dieter's illustrations were published after his death, they were used to support the reticular theory, proponents of which argued that the nervous system is composed of a continuous network of axons and dendrites.

Support for the reticular theory continued after the development of the black reaction by Golgi. In 1873 in Abbiategrasso, Italy, Golgi developed the black reaction, which allowed for the complete viewing of neurons for the first time. Golgi found that silver salts such as silver nitrate could be used to dye neurons, making their structures easier to identify. Similar to Deiters' technique, Golgi first used a potassium dichromate solution to harden the tissue, then he immersed the tissue in a silver nitrate bath. The silver nitrate reacted with the potassium dichromate to form fragments of silver chromate on the cell membrane, staining it black. Only one to five percent of neurons per sample tissue were stained using this technique. The selective staining of neurons allowed scientists to view an entire neuron without inflicting any damage to cell or obscuring its visibility.

Using the black reaction to study neural tissues, in 1887 at the University of Barcelona, in Barcelona, Spain, neuroscientist Ramón y Cajal noted that the terminal ends of the neuron fibers did not form a network of continuous fibers. Instead the ends remained free and made temporary contact with the surrounding neurons. Ramón y Cajal hypothesized that those neuron fibers allowed nerve cells to communicate with each other but not be functionally dependent on them. Ramón y Cajal suggested that neural bodies are not connected with a continuous network of axons and dendrites. Rather, neural bodies function independently of one another with gaps in between. Those gaps, later known as synapses, discredited the reticular theory and influenced the formation of the neuron doctrine. The existence of a synapse, or a junction that plays a role in the communication between two cells, was later confirmed with the invention of the electron microscope, which made it possible to produce detailed images of neural structures.

Later, Physician Heinrich Wilhelm Gottfried von Waldeyer-Hartz first proposed the term neuron and the concept of the neuron doctrine in 1891 in his paper, "Ueber einige neuere Forschungen im Gebiete der Anatomie des Centralnervensystems (Schluss aus No. 49.)" (On Some Recent Research in the Field of Anatomy of the Central Nervous System (Conclusion from No. 49)). Waldeyer-Hartz used the observations of other scientists to support his claim that the neuron is the most basic structural unit of the nervous system. The acceptance of the neuron as an independent unit based to the identification of synapses using the black reaction, scientists were able to see neurons in great detail leading to the discovery of neural cellular structures, like the Golgi apparatus, and to confirm the neuron doctrine as compatible with cell theory.