Over the years, I have taught my copy of Microsoft Word a lot of neuroscience terminology: amygdala, corpus callosum, dendritic spines, voxel. But it always knew what neuron meant. I thought I did too.

Neurons—the electrically excitable cells that make up the brain and nervous system—first fascinated me in high school. In college, like so many other students studying the brain, I dutifully memorized the structure of the archetypal neuron. I also remember learning about a few different types of neurons with different shapes and functions: motor neurons that make muscles twitch, for example, and unique sensory neurons in the eyes and nose.

Only recently, however, have I begun to recognize and appreciate the extraordinary diversity of cells in the nervous system—cells that differ from one another more than the cells of any other organ. Some neurons send electrical signals along fibers that stretch several feet; other neurons' branches extend only a few millimeters away from the cell body. Some neurons possess a fractal beauty similar to that of ferns and corals: Purkinje cells, for example, often sport finely branched nets, like a sea fan. But some of their neighbors look more like tangled tumbleweeds. One neuron might appear more or less round under the microscope—like a firework frozen in climax—whereas another might spider through the brain like a daddy longlegs. Neurons not only differ in shape—different types of neurons turn on different sets of genes and not all neurons use the same chemicals to communicate. Excitatory neurons mostly stimulate other cells; inhibitory neurons prefer to stifle. Most neurons fire in patterns, but their tempos vary: some keep a steady beat, others remain largely silent except for the occasional burst of activity and still other cells continually fire like a trigger-happy toddler playing laser tag. To summarize: not all neurons are exactly alike. The brain contains multitudes.

The Know Your Neurons series will celebrate and explore the cellular diversity of the nervous system, which is a subject of active research today. In the last decade, for example, intriguing and ostensibly unique types of neurons—such as spindle neurons and mirror neurons—have soaked up the spotlight because these cells might be crucial for some of the brain's most sophisticated forms of intelligence. However, scientists have not yet reached consensus about just how special these cells really are. In decades to come, increasingly powerful imaging technologies will allow researchers to see neurons in greater detail than ever before, likely revealing previously hidden differences between brain regions and cell types. Close inspection is how the neuron was discovered in the first place. It took years of careful observations to convince the scientific community that neurons were true cells.

The Discovery and Naming of the Neuron

The word neuron, as we understand it today, did not exist before 1891.

By the middle of the 19th century, scientists had discovered that the tissues of plants, animals and all living things were made of discrete units called "cells," the same "small rooms" that 17th century English physicist Robert Hooke observed in a slice of cork under his microscope. However, one kind of living tissue appeared to be an exception to "cell theory"—the nervous system.

When the leading anatomists of the 19th century examined fragile nervous tissue with the best microscopes available to them, they identified cell bodies that sprouted many tangled projections. German histologist Joseph Gerlach's observations convinced him that the fibers emerging from different cell bodies fused to form a continuous network, a seamless web known as the "reticulum." His ideas were popular. Many researchers accepted that, unlike the heart or liver, the brain and nervous system could not be split up into distinct structural units.

In 1873, Italian physician Camillo Golgi discovered a chemical reaction that allowed him to examine nervous tissue in much greater detail than ever before. For some reason, hardening a piece of brain in potassium dichromate, and subsequently dousing it with silver nitrate, dyed only a few cell bodies and their respective projections in the tissue sample, revealing their complete structures and exact arrangement within the unstained tissue. If the reaction had stained all the neurons in a sample, Golgi would have been left with an unfathomable black blotch, as though someone had spilled a bottle of ink. Instead, his technique yielded neat black silhouettes against a translucent yellow background.

Golgi's "black reaction," combined with the painstaking work of Karl Deiters and others, clearly distinguished two kinds of projections from cell bodies in nervous tissue: a long slender cable that did not seem to branch much and a cluster of shorter branching fibers. Even though Golgi saw that one cell body's branching fibers did not fuse with another's, he did not reject Gerlach's idea of the reticulum—instead, he decided that the long slender cables probably connected to form one continuous network.

Fourteen years later, in 1887, Spanish neuroanatomist Santiago Ramón y Cajal learned about Golgi's black reaction from psychiatrist Luis Simarro Lacabra, who had managed to improve Golgi's original technique. Cajal, who was already obsessed with studying the structures of living tissues in minute detail, immediately recognized the black reaction as the most sophisticated way to investigate the nervous system and puzzled at why so few scientists apart from Golgi himself had tried out the staining procedure. Cajal further improved the black reaction and applied the technique to all kinds of nervous tissue from different animals and from people, producing beautiful and detailed sketches of what he saw under the microscope—drawings that scientists and educators still rely on today.

Cajal's studies showed that, contrary to Golgi's suspicion, the long slender cables emerging from cell bodies did not fuse into one mesh. Although the many fibers in a tissue sample overlapped, they remained distinct physical structures, like interweaving branches of different trees in a crowded forest. There was no reticulum. The nervous system, like all other living tissue, was made up of discrete building blocks, or what Cajal called "absolutely autonomous unit[s]."

In October 1889, Cajal visited the Congress of the German Anatomical Society in Berlin to present his findings to the world's leading neuroanatomists. Although many scientists had mocked Cajal and his sketches, his presentation in Germany convinced the extremely influential Swiss histologist Rudolf Albert von Kölliker to abandon any notion of the reticulum. In 1891 German anatomist Wilhelm Waldeyer synthesized Cajal's groundbreaking research with the cell theory of the 1830s—adding ideas introduced by Swiss embryologist Wilhelm His and Swiss psychiatrist August Forel—to form the "neuron doctrine": the nervous system is made up of discrete cells, which Waldeyer dubbed neurons. In 1896, Rudolph Albert von Kolliker coined the term axon to describe the long slender cables that transmit signals away from cell bodies. In 1889, William His named the thin branching fibers that ferry signals toward the cell body dendrites. Based on his drawings of cellular circuits, Cajal had already inferred the direction in which signals moved through neurons.

Cajal's sketches remain of one the most detailed accounts of the structural diversity of the brain and nervous system. Today, we know that although brain cells are built from a common blueprint, they differ from one another structurally, functionally and genetically. One could even argue that, because each neuron links up with neighbors in its own way, every single cell in the brain is unique. Next on Know Your Neurons, we explore the different ways to classify brain cells and try to get a sense of just how many different types exist.


Bentivoglio, M. Life and Discoveries of Santiago Ramon y Cajal. Nobelprize.org. 1998. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1906/cajal-article.html

Costandi, M. The discovery of the neuron. Neurophilosopy. 2006. http://neurophilosophy.wordpress.com/2006/08/29/the-discovery-of-the-neuron/

Kandel ER, Schwartz JH, Jessell TM 2000. Principles of Neural Science, 4th ed. McGraw-Hill, New York

Mazzarello, P. A unifying concept: the history of cell theory. Nature Cell Biology 1, E13 - E15 (1999) doi:10.1038/8964

Schoonover, Carl. 2010. Portraits of Mind. Abrams.