Featured Grant Research

Timothy Holy awarded R01 grant to investigate mouse pheromones

For animals such as mice, olfaction is their primary route to pick up social information, whether that’s identifying the dominant male in a group or figuring out the reproductive status of females. In turn, these signals can influence animals’ behavior and physiology. Pheromones in male urine, for instance, can trigger early puberty in mice. While these compounds deliver critical intel, the mechanism for how an olfactory cue is sensed, processed and integrated into a socially relevant behavior remains largely unknown.

Tim Holy
Tim Holy, PhD

Timothy Holy, PhD, the Alan A. and Edith L. Wolff Professor of Neuroscience at Washington University School of Medicine, has received $2.1 million from the National Institutes of Health to fill in the gaps in knowledge about pheromone signaling. These insights could illuminate the neural pathways responsible for transforming sensory information into behavior, and in particular, point to how the environment can affect endocrine status and puberty—a known phenomenon in humans as well as mice.

The project stems from an observation made half a century ago that pheromones influence reproductive status. In mice, male urine accelerates puberty and induces estrus in females. Yet the identity of the compounds responsible for these profound effects remained unknown for decades.

Recently, Xiaoyan Fu, PhD, a staff scientist in the Holy Lab, led experiments that homed in on two novel compounds in male urine that trigger responses in neurons in the mouse vomeronasal organ, which detects pheromones. The new grant will fund continued exploration into these compounds, to identify the receptors on vomeronasal neurons that respond to them and trace the downstream neural circuitry responsible for integrating these signals into behavioral outputs.

Xiaoyan Fu
Xiaoyan Fu, PhD

The research will also address an outstanding mystery of pheromone signaling: how are non-volatile compounds, such as the two Fu identified, detected? “There’s no sensing at a distance,” says Holy. “This is an olfactory system, but sampling requires direct physical contact.” One hypothesis they will test is whether a volatile component of the pheromone breaks off to signal to the animal to inspect the source.

Holy notes that the project offers a unique opportunity to track an environmental cue through to its behavioral consequence. “There are very few examples anywhere in animal behavior where there’s a reasonable hope of chasing the sensory inputs through the computations that the animal executes and all the way to the decision-making and behavioral output circuity, especially in a mammal,” says Hold. “There are very few cases where we can do that for a socially relevant behavior. And here, there’s a plausible chance to pull it off.”