The Neuron Doctrine

Overcoming Obstacles in Brain Cell Study

To study the structure of brain cells, scientists have had to overcome several obstacles. Neurons cannot be seen by the naked eye, so cellular neuroscience could not progress before the development of the compound microscope in the late seventeenth century. Early in the nineteenth century, scientists discovered how to harden, or “fix,” tissues by immersing them in formaldehyde, and they developed a special device called a microtome to make very thin slices. The final breakthrough in neurohistology was the introduction of stains that selectively color some, but not all, parts of the cells in brain tissue.

Introduction of the Nissl Stain

One stain still used today was introduced by the German neurologist Franz Nissl in the late nineteenth century. Nissl showed that a class of basic dyes would stain the nuclei of all cells as well as clumps of material surrounding the nuclei of neurons. These clumps are called Nissl bodies, and the stain is known as the Nissl stain. The Nissl stain is extremely useful for two reasons: It distinguishes between neurons and glia, and it enables histologists to study the arrangement, or cytoarchitecture, of neurons in different parts of the brain.

Discovery of Neuronal Structure with Golgi Stain

A Nissl-stained neuron looks like little more than a lump of protoplasm containing a nucleus. Neurons are much more than that, but how much more was not recognized before Italian histologist Camillo Golgi devised a new method. In 1873, Golgi discovered that soaking brain tissue in a silver chromate solution, now called the Golgi stain, makes a small percentage of neurons become darkly colored in their entirety. This revealed that the neuronal cell body is actually only a small fraction of the total structure of the neuron.

Detailed Neuronal Anatomy Revealed

The Golgi stain shows that neurons have at least two distinguishable parts: a central region that contains the cell nucleus and numerous thin tubes that radiate away from the central region. The swollen region containing the cell nucleus has several names that are used interchangeably: cell body, soma, and perikaryon. The thin tubes that radiate from the soma are called neurites and are of two types: axons and dendrites. The cell body usually gives rise to a single axon. The axon is of uniform diameter throughout its length, and any branches from it generally extend at right angles. Dendrites, on the other hand, are rarely longer than 2 mm. Many dendrites extend from the cell body and generally taper to a fine point. Early histologists recognized that because dendrites come in contact with many axons, they must act as the antennae of the neuron to receive incoming signals, or input.

The Debate Between Golgi and Cajal

Golgi and Cajal drew completely opposite conclusions about neurons. Golgi championed the view that the neurites of different cells are fused together to form a continuous reticulum, or network, similar to the arteries and veins of the circulatory system. Cajal argued forcefully that the neurites of different neurons are not continuous with each other and communicate by contact, not continuity. This idea that cell theory also applies to neurons came to be known as the neuron doctrine.

Validation of the Neuron Doctrine

The scientific evidence over the next 50 years strongly supported the neuron doctrine, but final proof had to wait for the electron microscope in the 1950s. With the increased resolving power of the electron microscope, it was finally possible to show that the neurites of different neurons are not continuous with one another. Thus, our starting point in the exploration of the brain must be the individual neuron.

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