How mice smell fear

Mysterious structure at the tip of the nose could be a special alarm sensor.

Fear stinks. And its stench tickles a recently re-discovered set of nerves in the tip of a mouse’s nose.

FEAR-OMONE | The Grueneberg ganglion, composed of about 500 neurons, is an alarm pheromone sensor. Science/AAAS

Swiss researchers report in the Aug. 22 Science that they have finally found a function for a structure called the Grueneberg ganglion. The structure, composed of about 500 neurons, is an alarm pheromone sensor, say Marie-Christine Broillet, a neurophysiologist at the University of Lausanne, and her colleagues.

“It’s an interesting paper and something the field has been waiting for, to know what these cells are doing,” comments Minghong Ma, a neuroscientist at the University of Pennsylvania School of Medicine in Philadelphia.

Alarm pheromones are mysterious substances given off by animals under stress. The chemicals — no one really knows exactly what mammalian alarm pheromones look like — signal other members of a species that something bad is happening. Animals typically respond to the signals by running away, freezing (so predators won’t notice them) or attacking, Broillet says.

Researchers have yet to identify the source of the alarm pheromones in mammals and until now had no idea how mice, humans and other animals detected chemical fear cues.

First described in 1973, the Grueneberg ganglion was largely forgotten until a few years ago when mice were genetically engineered to produce a green fluorescent protein in their neurons, Broillet says.

Scientists were surprised to see the clusters of green neurons sitting all alone at the tip of the mice’s noses. The Grueneberg ganglion sends long projections, called axons, to the brain’s scent-processing center. But the ganglion is separate from other odor and pheromone-sensing structures and its function was unknown.

The structure is fully developed at birth, so some researchers believe it is involved in helping mothers and pups recognize each other. But the new study found that neurons in the ganglion don’t respond to milk or other mammary secretions. The neurons are also oblivious to odors, known mouse pheromones, urine, temperature, pressure and acidity.

Because the Grueneberg ganglion didn’t respond to anything the team tried, the researchers decided to look at its structure instead.

“We learned a lot from the electron microscopy,” Broillet says. The neurons in the Grueneberg ganglion are covered with skin, have cilia — fingerlike projections often found on scent-detecting cells — and are wrapped with support cells called glia. The skin and wrappings shield the cells from direct contact with irritants.

“It’s a dangerous world out there,” says Charles Derby, a chemical ecologist and neuroscientist at GeorgiaStateUniversity in Atlanta, who studies chemical sensing in spiny lobsters. “You need your sensors out there interacting with the environment, but you also need protection.”

Such protective measures mean the cells probably detect volatile, water-soluble substances that can pass through the protective barrier. Alarm pheromones fit the bill. The Swiss researchers collected alarm cues from mice dying of carbon dioxide poisoning. Those alarm chemicals sparked activity in Grueneberg ganglion cells, and affected other mice’s behavior. Normal mice ran away from a tray of water containing the alarm pheromones and froze in the corner. Mice that had surgery to remove the ganglion continued exploring as if they were blind to the smell of fear, but had no trouble locating an Oreo cookie hidden in bedding.

Not everyone is convinced that the Grueneberg ganglion actually detects alarm pheromones.

“I don’t think that their ‘alarm pheromone’ is a pheromone,” says Yasushi Kiyokawa, a veterinary researcher at the University of Tokoyo who studies alarm pheromones in rats. The signal could be a non-specific odor given off by dead and dying animals. “However, I am convinced that this organ detects some aversive odor in mice.”

Humans have a Grueneberg ganglion. But other structures that humans and rodents share detect pheromones and odors for rodents, but don’t work in people, Ma says. Rodents are visually challenged so they rely on their sense of smell. But humans have language. “We probably yell out instead of waiting for a chemical signal,” she says.

Fear-omone from Science News on Vimeo .

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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