Know Your Neurons: How to Classify Different Types of Neurons in the Brain’s Forest

By Ferris Jabr | May 16, 2012 | Scientific American

Scientists have organized the cells that make up the nervous system into two broad groups: neurons, which are the primary signaling cells, and glia, which support neurons in various ways. The human brain contains around 100 billion neurons and, by most estimates, somewhere between 10 to 50 times as many glial cells.

All these cells are packed into a three-pound organ about the size of both your fists stuck together. You can think of your brain as a dense forest—the neuron forest—in which different kinds of trees grow near, around and on top of one another, their branches and roots intertwining. Just as all trees share a basic structure—roots, trunk, branches—but do not look exactly alike, all neurons are variations on a common structural theme. The diversity of structures is extraordinary and scientists are still discovering brain cells that do not really look like any brain cell they have seen before.

Different Types of Neurons (click to enlarge). A. Purkinje cell B. Granule cell C. Motor neuron D. Tripolar neuron E. Pyramidal Cell F. Chandelier cell G. Spindle neuron H. Stellate cell (Credit: Ferris Jabr; based on reconstructions and drawings by Cajal)

A model neuron. Click to enlarge (Credit: LadyofHats, Wikimedia Commons)

Before exploring the brain’s cellular diversity, let’s look at a model neuron. A typical neuron has three main structures: the cell body, the axon and the dendrites. The cell body contains the nucleus, which stores the cell’s genes; the axon is a long slender cable that carries electrical signals known as action potentials away from the cell body toward other neurons; and the dendrites are shorter branching fibers that receive signals from other neurons. Near its end, the axon of one neuron branches and forms connections with as many as 1,000 other neurons—but, as 19th century neuroanatomist Santiago Ramón y Cajal insisted, the end of one neuron does not fuse with the beginning of another into a seamless web. Instead, an axon’s branching tips communicate with the dendrites, axons and cell bodies of other neurons across tiny gaps called synapses.

Neurons classified by structure. Click to enlarge (Credit: Ferris Jabr)

Scientists have classified neurons into four main groups based on differences in shape. Multipolar neurons are the most common neuron in the vertebrate nervous system and their structure most closely matches that of the model neuron: a cell body from which emerges a single long axon as well as a crown of many shorter branching dendrites. Unipolar neurons, the most common invertebrate neuron, feature a single primary projection that functions as both axon and dendrites. Bipolar neurons usually inhabit sensory organs like the eye and nose. Their dendrites ferry signals from those organs to the cell body and their axons send signals from the cell body to the brain and spinal cord. Pseudo-unipolar neurons, a variant of bipolar neurons that sense pressure, touch and pain, have no true dendrites. Instead, a single axon emerges from the cell body and heads in two opposite directions, one end heading for the skin, joints and muscle and the other end traveling to the spinal cord.

Neurons classified by function. Click to enlarge (Credit: Ferris Jabr)

Researchers also categorize neurons by function. Sensory neurons collect information from sensory organs—from the eyes, nose, tongue and skin, for example. Motor neurons carry signals from the brain and spinal cord to muscles. Interneurons connect one neuron to another: the long axons of projection interneuons link distant brain regions; the shorter axons of local interneurons form smaller circuits between neighboring cells.

Do these basic classes account for all types of neurons? Well, just about every neuron in the human nervous system should fall into one these broad categories—but these categories do not capture the true diversity of the nervous system. Not even close. If you really want to catalogue neurons in their many forms—somewhat like the way scientists have classed living things into families and species and subspecies—you’re going to need a lot more categories. Neurons differ from one another structurally, functionally and genetically, as well as in how they form connections with other cells. In some ways, it’s up to you how far you want to take this. Some people are content with a few broad categories and do not see a need to identify and categorize every single type of neuron. Others are fascinated by the differences between cells in the brain and nervous system, even the subtlest distinctions. Some are fascinated for practical reasons, because some of these differences help explain, for example, why certain diseases only harm a certain population of neurons. Others are motivated by pure curiosity.

Since at least the 19th century—even before Cajal convinced the leading anatomists of the time that the nervous system was made of discrete cells—scientists recognized that not all components of the nervous system looked the same and began differentiating these components by name. In 1840, Adolphe Hannover discovered what today we call the ganglion cells of the retina, the light-sensitive tissue at the back of the eye. In 1866, Leopold August Besser named large, densely branching neurons “Purkinje cells” after their discoverer, Czech anatomist Jan Purkyně. Vladimir Alekseyevich Betz discovered the largest cells in the central nervous system, today known as Betz cells. Cajal tried out various names for different kinds of neurons, as well as their tinier features. He called little bumps along the length of dendrites espinas, the Spanish word for thorns. Today, we call them dendritic spines.

So how many different types of neurons have scientists named so far? To find out, I contacted several neuroscientists who specialize in cell biology and what you could call neuron taxonomy. Perhaps unsurprisingly, no one has an exact number, but if you count all the types and subtypes in the entire nervous system, the answer is at least in the hundreds. One great resource for exploring the cellular diversity of the nervous system is NeuroMorpho.org, a database of digitally reconstructed neurons that you can browse by species, brain region and cell type. Check out the Cell Typespage and you’ll encounter descriptive names like cone cell, climbing fiber, crab-like, medium spiny cell, pyramidal cell, chandelier cell and tripolar cell—each of which boasts a unique structure. 3D models of these neurons pop into view when you mouse over the file names of different reconstructions.

Gordon Shepherd of Yale University pointed me to the Neuroscience Lexicon, a database that he and his colleagues are building. Take a look for yourself at their current list of types of neurons. Here’s what the Lexicon lists for distinct types of neurons in the cerebellum, an evolutionarily ancient part of the brain that helps coordinate movement:
• Cerebellum Golgi cell
• Cerebellum Lugaro cell
• Cerebellum Purkinje cell
• Cerebellum basket cell
• Cerebellum candelabrum cell
• Cerebellum granule cell
• Cerebellum nucleus reciprocal projections neuron
• Cerebellum stellate cell
• Cerebellum unipolar brush cell

And that’s just one region of the brain. Remember that the human brain contains around 100 billion neurons densely packed into three-pounds of tissue. Consider that the human brain is one of the most complex structures we have ever tried to understand. All those layers of fragile, excitable tissue folded upon one another. Within those folds we will surely discover new types of neurons of which we have no inkling at present.