A Game of Cat and Mouse? Olfactory Nerve Plays Role in Animal's Escape

Researchers have found that a small smell may help a mouse escape from a risky feline. A Northwestern University study involving olfactory receptors, which underlie the sense of smell, provide evidence that a single gene is necessary for the behavior.

Led by neurobiologist Thomas Bozza, researchers have found that one olfactory receptor from mice has a profound effect on behavior. The gene, called TAAR4, helps encode a receptor that responds to a chemical that is enriched in the urine of carnivores. As mice avoid the scent marks of predators, mice lacking the TAAR4 receptor do not.

Researchers note that unlike our sense of vision, much less is known about how sensory receptors contribute to the perception of smells. For instance, color vision is generated by the cooperative action of three light-sensitive receptors found in sensory neurons from the eye, but people with mutations in even one of these receptors experience blindness.

"It is easy to understand how each of the three color receptors is important and maintained during evolution," said Bozza, an author of the paper, according to a press release, "but the olfactory system is much more complex."

However, researchers believed that a mutation in the olfactory nerve would not cause such a similar distinction.

"The general consensus in the field is that removing a single olfactory receptor gene would not have a significant effect on odor perception," said Bozza, an assistant professor of neurobiology in the Weinberg College of Arts and Sciences.

Bozza and his colleagues tested this assumption by genetically removing a specific subset of olfactory receptors called trace amine-associated receptors, or TAARs, in mice. Mice have 15 TAARs. One is expressed in the brain and responds to amine neurotransmitters and common drugs of abuse such as amphetamine. The other 14 are found in the nose and have been coopted to detect odors.

Bozza's group has shown that the TAARs are extremely sensitive to amines -- a class of chemicals that is ubiquitous in biological systems and is enriched in decaying materials and rotting flesh. Mice and humans typically avoid amines since they have a strongly unpleasant, fishy quality.

Bozza's team, including the paper's lead authors, postdoctoral fellow Adam Dewan and graduate student Rodrigo Pacifico, generated mice that lack all 14 olfactory TAAR genes. These mice showed no aversion to amines. In a second experiment, the researchers removed only the TAAR4 gene. TAAR4 responds selectively to phenylethylamine (PEA), an amine that is concentrated in carnivore urine. They found that mice lacking TAAR4 fail to avoid PEA, or the smell of predator cat urine, but still avoid other amines.

"It is amazing to see such a selective effect," Dewan said. "If you remove just one olfactory receptor in mice, you can affect behavior."

The TAAR genes are found in all mammals and researchers from the study note that they hope for this will reveal new information about brain circuits in other mammals, possibly even humans.

Findings for the study are from the April 28 issue of the journal Nature.