Scientists elucidate pheromone operation

The enigmatic ways in which some animals communicate via chemicals just became a little clearer.

Duke scientists published a study in the journal Science last week which found that the brain's response to chemicals called pheromones in mice are much more specific than previously thought--a finding that challenges traditional views of pheromone processing and could change the direction of future research.

The study, which was conducted by James B. Duke Professor of Neurobiology Lawrence Katz, postdoctoral fellow Minmin Luo and Michale Fee of Bell Laboratories, focused on the connections between specific pheromones and how the brain interprets them.

"The results were quite shocking," Luo said. "Each cell has a highly selective response, and we expected to see less of that."

While most non-human mammals use pheromones--chemicals that are given off by specific individuals to communicate social and reproductive information--little is known about the processing system itself or how it creates a "pheromonal image" of another animal.

"We use face recognition in primates as a metaphor for the function of pheromones," Katz said. "Humans and other primates use visual cues such as the eyes and mouth to identify specific individuals according to gender and other characteristics, whereas mice are non-visual animals. They rely on a rich palette of chemicals to enable them to make these distinctions."

Researchers outfitted test mice with ultraminiature electrodes, designed by Fee, which measured the rate of impulses of different neurons in the accessory olfactory bulb, the area in the brain thought to process incoming pheromones.

A male test mouse was introduced into a test arena along with a stimulus mouse, which had been lightly anesthetized to prevent fighting or mating. Stimulus mice came from a variety of mouse strains and could be either male or female. The test animal was allowed to explore the stimulus animal while electrodes recorded neuronal impulses.

The study demonstrated that pheromones enter a specific part of the animal's nasal passage, called the vomeronasal organ, by a pumping system that only activates when pheromones are directly present.

"We found that the acquisition of pheromones requires direct contact; the nose must touch the body of the stimulus in order for pumping to begin," said Luo. In addition, though it was traditionally thought that the anus and genitals were most important for pheromone release, the study found that contact with the face region also stimulated the pumping mechanism.

However, the most unexpected finding was the amount of specificity in the neuronal responses, meaning that each sensor was activated or inhibited exclusively by a corresponding strain and sex. For example, no single sensor generalized to all female or all male mice.

It is still unclear whether there is an area of the brain that integrates the pheromonal information into a more general signal--like the face recognition mechanism in primates--or whether the signals remain in pieces much like an unfinished "jigsaw puzzle of information," Katz said.

"The results are quite significant," said Michael Meredith, professor and director of the Chemosensory Training Program at Florida State University. "We didn't previously have much information on the workings of the vomeronasal system. It's a very difficult experiment--I've tried similar ones and they're not easy--but they carried it out in a way that gave clear results."

The study is just the tip of the iceberg for research in the field of pheromone processing. The researchers plan studies to examine just how pheromones affect behaviors such as aggression, mating and reproduction.

Specifically, they will look at the memory formation of individuals' social hierarchies and previous mates. "It's an exciting avenue. We might be able to watch memories in the process of being created," Katz said.

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