Fu Xiaoyan, Yan Yuetian, Xu Pei S, Geerlof-Vidavsky Ilan, Chong Wongi, Gross Michael L, Holy Timothy E
Department of Anatomy and Neurobiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
Department of Chemistry, Washington University in St. Louis, St. Louis, MO 63110, USA.
Cell. 2015 Oct 8;163(2):313-23. doi: 10.1016/j.cell.2015.09.012. Epub 2015 Oct 1.
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.
在哺乳动物的社交互动中,个体通过嗅觉线索被识别,但在数千种化合物中识别关键信号仍然是一项重大挑战。为满足这一需求,我们开发了一种新技术,即成分-活性匹配(CAM),以选择能够“解释”各种复杂混合物生物活性模式的候选配体。利用来自八个不同性别和品系的小鼠尿液,我们确定了23种成分来解释犁鼻器感觉神经元八个功能类别中七个类别的放电率。聚焦于一类对雌性有选择性的神经元,我们鉴定出了一个新的犁鼻器配体家族,即类固醇羧酸。这些配体解释了一些雌性品系尿液的大部分神经元活性,是雄性对雌性气味进行探究行为正常水平所必需的,并且足以引发交配行为。CAM代表了朝着详尽表征哺乳动物嗅觉系统中自然行为的分子线索迈出的第一步。