Mice have a sharp nose for pheromones

Most animals have two noses. That is, they have a set of sensory nerve cells that detects the world’s myriad smells and another that reacts to pheromones, the elusive chemicals that drive reproductive behavior within many species.

Although biologists have recently revealed how mammals recognize traditional scents, they’ve lagged behind in understanding pheromone processing. In the June 15 Nature, however, a research team reports that the mouse neurons that perceive pheromones do so with extraordinary sensitivity and in a way distinct from that of the main olfactory system.

“It is the best story on the biology of mammalian pheromones that I have seen in a long time,” says olfaction researcher Peter Mombaerts of Rockefeller University in New York. Mice and other mammals detect pheromones with their vomeronasal organ (VNO), sensory tissue that resides in the nasal cavity but is separate from the main olfactory neurons. In the new work, Frank Zufall of the University of Maryland School of Medicine in Baltimore and his colleagues exposed living slices of mouse VNOs to six putative pheromones that other researchers had isolated from mouse urine. Some of the compounds, for example, alter the timing of puberty or induce female sexual behavior.

In one series of experiments, the investigators measured electrical activity within the VNO and showed that each of these chemicals could stimulate the firing of VNO neurons. They also isolated individual nerve cells and exposed them to the pheromones one at a time. Just 3 of 52 cells responded, each to a different pheromone.

Zufall’s team next imaged the response of the VNO by adding a calcium-activated fluorescent dye to its cells. Using a microscope to monitor hundreds of neurons at a time, the investigators could see single neurons light up as they reacted to a pheromone by taking in calcium.

“This is an enormous step,” says Catherine G. Dulac of Harvard University. The sensitivity of mouse VNO neurons to certain pheromones was 1,000 to 10,000 times greater than that of the main olfactory nerve cells to perceptible smells. “Absolutely amazing,” says Dulac, noting that the pheromone sensitivity of mice matches that of insects.

Last year, scientists confirmed that mammals’ main olfactory system uses a combinatorial approach to identify smells (SN: 4/10/99, p. 236). Each sensory nerve cell responds to many odorants, and a single odorant stimulates multiple receptors, the cell-surface proteins that recognize a chemical.

The VNO apparently doesn’t work that way. Zufall’s team found that individual neurons there respond only to a single pheromone and that only a few of the VNO’s nerve cells, perhaps 1 percent, detect any single pheromone.

“The principles for processing chemical information are very different in this tissue,” says Zufall.