Dulac was surprised to find that most VNO neurons were activated by predator cues and not by mouse cues. “The animal doesn’t need a lot of receptors to identify another mouse, but it needs a lot of receptors to be able to detect many, many types of predators,” she says.

Some receptors were very specialized, activated only by a particular snake, bird of prey, or mammalian predator. Others were more generalized, responding to an entire class of predators (for example, all snakes). Some were even more generalized and detected all predators.

Another surprising finding was the receptors’ extreme specificity. “We rarely saw receptors that were activated by both predator and mouse cues,” says Dulac. Thus, activation of a single receptor is enough to identify the animal giving off the chemosensory signal. Dulac likens it to a switchboard, where the switch you push tells you very precisely what type of animal is being encountered.

This is the most recent experiment in Dulac’s long line of research challenging the assumptions about pheromones and the role of the VNO. After identifying the first family of pheromone receptors and other molecules unique to VNO neurons, in 1995, she began investigating the role of the VNO in mouse social behavior. What she discovered upended much of the conventional wisdom about pheromones and sexual behavior.

She discovered, for instance, that male mice whose VNO function had been genetically knocked out failed to display stereotypical aggression toward other males and attempted to mate with both male and female mice. “This indicated the VNO does indeed detect pheromones, but these pheromones aren’t essential for mating,” Dulac says. “They are necessary for sex discrimination.”

		In wild type CD-1 mice, the soiled bedding of rats elicits defensive behaviors such as avoidance. Mice whose vomeronasal activity is genetically ablated (TrpC2-/-) no longer avoid rat bedding and instead feed on it.

A similar experiment with female mice revealed that those with nonfunctional VNOs behaved more like males in their sexual and courtship behaviors. The results suggested that the brains of female mice are hard-wired with the same neuronal circuits that underlie male-specific behaviors, but the VNO acts to inhibit male behaviors and activate female ones.

Now that Dulac has identified the chemical signals detected by the VNO and the specific receptors involved, she can manipulate the system to learn how the brain processes sensory information and translates it into a behavioral response. This work opens up questions about learning and identification. Are prior encounters with a signal necessary to recognize it, or is there an innate recognition of predators and members of one’s own species? Dulac is excited about the possibilities and hopes these results will add to scientists’ arsenal of tools for understanding how animals detect, identify, and process sensory signals.

“A central question in neuroscience is how animals are able to tell apart different types of sensory signals,” Dulac says, “regardless of whether they come from the nose, ears, or eyes. What we learn from the chemosensory system in mice may tell us about the principles of neural circuits between sensory systems and the brain more generally.”

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