Researchers are mapping the chemical signaling behind how mice detect friend and foe.

Catherine Dulac and colleagues have discovered how the mouse vomeronasal organ (VNO)—a specialized organ used by reptiles and most mammals to detect nonairborne scents—helps the animals identify predators as well as other mice. A spectrum of colors in this image highlights the VNO’s different sensory neurons, each detecting a unique social or defensive cue.

Mice lead complex social lives. During the course of a day, they may come across other members of their own species—male or female—or any number of predators. Each encounter requires a specific behavioral response.

Unlike humans, mice don’t perform these daily discriminations visually. Instead, they depend on chemical cues in the form of scents and other odors, such as pheromones.

Catherine Dulac, an HHMI investigator at Harvard University, studies the molecular logic underlying the coding of odorant- and pheromone-mediated signals. Dulac is uncovering how connections form between sensory neurons and the brain and how these circuits allow an animal to discriminate a potential mate, a harmless acquaintance, or a predator.

In recent work, Dulac advanced understanding of the function and architecture of the vomeronasal organ (VNO), a structure at the base of the nasal cavity. By studying the response of neurons in the VNOs of mice to chemical cues collected from not just their kin but also rats, snakes, birds, and an assortment of other species, her research team discovered that the VNO is more geared toward detecting cues from predators than from other mice. The findings were published September 2011 in the journal Nature.

A rodent’s main olfactory system detects airborne odor molecules, while non-airborne signals—those left on physical objects by animals or humans, such as pheromones—are detected by the accessory olfactory system. In this accessory system, chemicals are sensed in the VNO, a tubular structure in the nose. Most mammals and reptiles have a VNO, but humans and some other primates appear to lack one.

The VNO houses tens of thousands of neurons, each equipped with receptors for a particular chemical cue. When a pheromone or other chemical signal arrives at the VNO, it fits into its matching receptor like a key in a lock, activating the neuron and sending a message to the brain. Dulac described the first VNO receptor while a postdoc in HHMI investigator Richard Axel’s lab some 15 years ago; since then, about 300 types of receptors have been identified. Yet, scientists had not worked out how many different chemical signals these receptors could detect, nor had anyone tried to map out the relationship between specific receptor types and the chemical signals to which they respond.

Dulac’s team set out to identify which particular VNO receptors were activated by a wide range of chemical cues. They devised an approach using the activation of certain genes as an indicator of neuronal activity.

First, mice were exposed to one of 29 chemosensory cues in the form of bedding from the cages of male and female mice and predators such as snakes and foxes. Bedding material absorbs a mix of chemicals excreted by animals, including urine, feces, saliva, and other gland secretions.

The researchers found that exposure to each individual pheromone from the bedding material activated neurons in the VNO sensitive to that particular chemical cue. They determined which receptor was expressed in the activated cells using 200 molecular probes developed for this purpose.

Image: Yoh Isogai and Catherine Dulac

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