A Molecular Code for Identity in the Vomeronasal System

• Published in: Cell 2015-10, Vol.163 (2), p.313-323
• Main Authors: Fu, Xiaoyan, Yan, Yuetian, Xu, Pei S., Geerlof-Vidavsky, Ilan, Chong, Wongi, Gross, Michael L., Holy, Timothy E.
• Format: Article
• Language: English
• Subjects: Animals; Chromatography, Liquid; Female; Male; Mice; Mice, Inbred Strains; Neurons - cytology; Neurons - physiology; Sex Attractants - chemistry; Sex Attractants - urine; Sexual Behavior, Animal; Smell; Species Specificity; Tandem Mass Spectrometry; Vomeronasal Organ - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2015.09.012

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. [Display omitted] •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 Component-activity matching (CAM), a technique for selecting candidate ligands that “explain” patterns of bioactivity across diverse complex mixtures, enabled the discovery of several new ligands that explain firing rates in functionally distinct classes of vomeronasal neurons, including a new set of ligands that are female sex pheromones for the mouse.