How many types of neurons do we need to define?

A recent perspective paper published in Science has raised some important, and timely, questions regarding neural diversity. The authors, from Columbia, MIT, and New York University, would simply like to know how many kinds of neurons exist in the brain. For scientists who study glial cells, it may be enough to have a single named class of neuron, but the researchers here all study motorneurons of one kind or another. In particular, they are interested in treating neurodegenerative diseases, which often have clear motor deficits as their major pathology. To treat these diseases, researchers are attempting to differentiate embryonic stem cells (ESCs) into particular cell subtypes that could be used to restore normal function. As the authors observe, it would be handy if we could constrain the enormous range of biochemical, morphological and electrophysiological peculiarities that neurons display, into well-defined categories that could be referred to by name.

The reality is that we cannot have a simple neuron taxonomy like we do, for example, with animals. Occasional hybrids aside, animal species are those that can produce fertile offspring when they mate. Name proliferation in neuroscience is instead open-ended, and the rate at which it occurs is its major parameter. It seems that we have moved beyond the age of the Neuro Rock Star, and honorifics might no longer be expected. While only a few additions to the classics—like the Betz cells of the motor cortex, Martinotti cells, and Cajal-Retzius cells—have managed to gain penetrance in neuroculture, there has been an explosion in potential ways to define neurons in terms of the kinds of genes and proteins that they are geared up to produce. What then is a suitable way to tame this new jungle?

With an eye toward practicality, perhaps the best way forward is to stick with good old structure-function criteria, and now begin to concentrate on the function part. While genes and proteins can be manipulated ad nauseum and shown to have various effects on the morphology of neurons, we still lack a good understanding of what taking on one of those few basic cell plans, as shown in the familiar picture above, can do for a cell in terms of function. If we are concerned about restoring function to diseased brains on a cell by cell basis, then lets ask a few questions not about how molecular players generate morphology, but rather what the function of that fairly familiar morphology might be, and use that as a basis for future name derivations.

In other words, without an understanding of why cell shape slides along the continuum from bipolar, to pseudo-unipolar, to multipolar or other variations on the near-far/dendrite-axon dichotomy, to meet functional energetic needs, purely biochemical naming schemes will remain largely sterile. We may know, for example, that that the main process of a unipolar neuron stands off of the cell body a few microns, while that of the bipolar cell runs through it, and that a spike may slow down a little in the latter, but without knowing the functional implications of swapping one for the other, we actually know very little.

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