A Molecule That Shapes the Senses

Like the image in a funhouse mirror, the cortex of your brain contains a distorted map of your body. This part of the brain connects with touch-sensing nerves. Neuroscientists call this the homunculus, for "little person," and its distortions reflect the sensitivity of various body parts. In humans, for example, more of the map is devoted to the fingertips than the shoulders. Now, for the first time, researchers have identified a molecule that redraws the lines on this map, at least in mice.

The find came as a surprise. Neuroscientist John Flanagan of Harvard University Medical School and his colleagues were examining the brains of mice genetically engineered to lack a gene for the ephrin-A5 protein. The protein helps to guide axons, the long extensions of neurons, in the brain, and the researchers expected that neuron patterns might be affected. At first glance, the touch-sensing region looked normal, but on closer inspection the team noticed some subtle but persistent differences in the mutant mouse brains.

In the body map of normal mice, whiskers and forepaws are enlarged compared to the rest of the body. When Flanagan and his colleagues stained the brains of mutant mice with a dye that labels the "musunculus," they found that the normal pattern was distorted: Certain whisker regions were consistently larger than normal, they report in the April issue of Nature Neuroscience, while others were smaller. In addition, the region hooked up to the forepaw was smaller in mutant mice.

Previous work had suggested that the amount of sensations from various parts of the body helps shape the homunculus. When scientists trimmed the whiskers of young mice, for example, the corresponding whisker-sensing region in the brain shrunk. In contrast, primate studies have shown that repeated touches to the fingers can increase the area devoted to fingertips.

But this find is the first evidence of a molecule that shapes the homunculus, says neuroscientist Dennis O'Leary of the Salk Institute. It's especially interesting, he says, that the missing protein produces "not a disruption of the map but a distortion." That suggests that other molecules set up the overall pattern, while ephrin-A5 helps fill in the details.