Cell
Volume 163, Issue 2, 8 October 2015, Pages 313-323
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Article
A Molecular Code for Identity in the Vomeronasal System

https://doi.org/10.1016/j.cell.2015.09.012Get rights and content
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Highlights

  • CAM is an approach to match candidate ligands and specific patterns of bioactivity

  • 23 compounds in mouse urine explain firing rates in 7 classes of vomeronasal neurons

  • Steroid carboxylic acids are a new family of vomeronasal ligands

  • Steroid carboxylic acids are female sex pheromones for the mouse

Summary

In social interactions among mammals, individuals are recognized by olfactory cues, but identifying the key signals among thousands of compounds remains a major challenge. To address this need, we developed a new technique, component-activity matching (CAM), to select candidate ligands that “explain” patterns of bioactivity across diverse complex mixtures. Using mouse urine from eight different sexes and strains, we identified 23 components to explain firing rates in seven of eight functional classes of vomeronasal sensory neurons. Focusing on a class of neurons selective for females, we identified a novel family of vomeronasal ligands, steroid carboxylic acids. These ligands accounted for much of the neuronal activity of urine from some female strains, were necessary for normal levels of male investigatory behavior of female scents, and were sufficient to trigger mounting behavior. CAM represents the first step toward an exhaustive characterization of the molecular cues for natural behavior in a mammalian olfactory system.

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