Clues to the human brain lie in whiskers of rats

Consider a rat's whiskers.

They're constantly being brushed, wiggled and snipped.


Like hair and fingernails, whiskers are made of dead cells. But they're connected to follicles that make them as sensitive as fingertips - and an important tool for scientists.

Researchers in labs across the country probe the rat's whisker-to-brain connections, hoping to learn more about our neural pathways. Their goal is to advance treatments for brain related disorders and unravel the mystery of how humans interpret the sensation of touch.


"There are all kinds of possibilities," said Thomas Woolsey, a Missouri neurologist whose research 35 years ago, as a Johns Hopkins medical student, sparked much of today's interest.

Researchers had been breeding rats and mice since the early 1800s and training them to crawl through mazes and tap on levers. But in 1970, Woolsey and one of his Hopkins teachers, Hendrick Van der Loos, published a study showing that each whisker on a rodent's face connects to a specific neuron. They found that brushing any whisker fires off a specific set of neurons - arranged in the rat's brain in neat, barrel-shaped packages.

The finding sparked "an explosion of research," said Daniel J. Simons, a researcher at the University of Pittsburgh School of Medicine.

Scientists say their work could lead to new technologies for controlling prosthetic limbs and advancing therapies for Alzheimer's, stroke, Parkinson's disease and other disorders.

"Things have really taken off in the past five or 10 years," said Christopher I. Moore, a neurobiologist at the Massachusetts Institute of Technology. He and colleagues publish 30 to 50 scientific papers annually on the rat whisker studies. They also meet at least once a year, at a "barrels" conference, to discuss the latest research.

"It's like trying to decipher a different language," said Asaf Keller, a neurobiologist at the University of Maryland School of Medicine and the co-author of a recent rat whisker study.

Woolsey's initial studies used mice. But researchers agree that their findings apply just as well to rats. And in a field that often requires connecting whiskers to electrodes, rats are the preferred tool for most neurological studies. "Rats are easier to train and handle," Moore said.

Sensitive follicles


The usefulness of the rat whisker is based in the animal's physiology. Rats have poor eyesight, but living underground and foraging at night, they use whiskers as probes, extending them forward up to two inches to assess their surroundings.

Rats have about 30 large whiskers and dozens of smaller ones. Although a rat whisker is made up of dead cells, it's embedded in a hair follicle known as a "blood sinus" that passes signals from the whisker to a neuron pathway. While the rat's brain is simpler than a human's, it's a good stand-in for research.

"Ours is a more complex system, but the basic plan is the same. The similarities are more compelling than the differences," Simons said.

In 1973, Woolsey and Van der Loos showed that snipping off a single whisker in the first few days of a rat's life affected the rodent's ability to learn and function. That meant rats had brains like humans that can adapt to change.

"You can take the whiskers off, and it's like taking a finger off early on in life and being left with four fingers instead of five. The brain makes adjustments early on," said Woolsey, now a neurology professor at Washington University in St. Louis.

The research continues.


Neural 'sounds'

This spring, Moore's team at MIT published findings suggesting that rats may hear with their whiskers. The study, published in the May issue of Neuron, showed that rat whiskers act like strings on a harp, sending neural signals to the brain the way that a harp string produces notes when plucked.

Specific whiskers are tuned to specific ranges of neural "sounds," the researchers found. Short whiskers are sensitive to high frequencies and long whiskers are sensitive to low frequencies. "Whether they hear with their whiskers is a good question. I'd say it's an open question at this point," Moore said.

In separate studies published last month in the journal Science, neurobiologists at Duke and the University of Maryland detailed experiments demonstrating the intricacies of the rat's signaling system.

At Duke, scientists trained rats to discriminate between a large opening and a small one, rewarding the animal with sugar water if it poked in the right direction when it found a large or small opening. They showed that when rats were busy making that choice they interpreted a signal - a brushing motion along the whisker - differently than rats not engaged in the task.

The rats busy discerning the size of an opening fired off detailed signals in their neurons, like the dim outline of an object appearing on a black-and-white TV screen. The untrained rats fired off brighter, but less detailed signals, like the flash of a camera, said David J. Krupa, the study's author.


In the Maryland study, researchers hooked electrodes to the whiskers of 10 rats and exposed them to gentle waves of electrical current to simulate the whiskers rubbing against sandpaper.

Analyzing readings from electrodes implanted in the rat's brains, they found that neurons fired off signals in predictable patterns, determined by the frequency of the electrical signals.

Lauren Jones, the study's lead author, said the results showed the amazing complexity of the process that occurs every time a rat whisker touches a surface. The findings apply to humans, too.

"It means you don't need a thousand neurons to interpret a signal from your environment. You can do it with one signal," Jones said. "It shows how beautiful and how powerful the brain is."