Investigating bile acid detection and processing in the mouse accessory olfactory system

项目摘要/摘要 脊椎动物进化出平行的嗅觉途径来支持它们的生存和繁殖。近年来，它已经 很明显，从早期分化的鱼类到人类，脊椎动物都保留了探测环境的能力 类固醇使用他们的嗅觉系统。在啮齿动物中，包括老鼠在内，副嗅觉系统富含类固醇- 敏感的嗅觉神经元，称为犁鼻感觉神经元。这些神经元对排泄的类固醇敏感，如 在尿液中发现雌激素，雄激素和糖皮质激素；我们实验室最近发现，这个系统还 对粪便中发现的胆汁酸表现出广泛的敏感性。胆汁酸是一类极其重要的分子， 对饮食脂肪吸收至关重要，但我们很少了解化学感觉系统如何利用胆汁酸信息来 影响动物的生理和行为。这项研究计划的目的是增加我们对 副嗅觉系统检测胆汁酸的机制及胆汁酸信息的空间表征 在大脑里。具体地说，这项拟议的研究将确定小鼠犁鼻感觉神经元对 粪便气味和几个相关的单分子胆汁酸配体，这将增加我们的广度和深度 了解感觉外周的粪便气味和胆汁酸检测。随后，粪便的突触终末- 在副嗅球的肾小球层分支的胆汁酸敏感神经元将在功能上 使用实时光片显微镜绘制了3维地图。最后，投射神经元对胆汁酸的敏感性，称为 直接定位于杏仁内侧核和终纹床核的二尖瓣细胞将被评估，确定 胆汁酸信息是如何分类到这些并行输出通道中的。结合起来，结果将显示胆汁酸是如何 由辅助嗅觉系统中的神经元以帮助塑造动物行为的方式进行编码和准备。这些数据 这将提高我们对大脑功能的理解，并将为进一步研究化学感觉提供基础 对哺乳动物社会和生殖行为的影响。

Project Summary/Abstract Vertebrates have evolved parallel olfactory pathways to support their survival and reproduction. In recent years it has become clear that vertebrates from early-diverged fishes to humans have retained the capacity to detect environmental steroids using their olfactory systems. In rodents, including mice, the accessory olfactory system is enriched in steroid- sensitive olfactory neurons, called vomeronasal sensory neurons. These neurons are sensitive to excreted steroids like estrogens, androgens, and glucocorticoids found in urine; our laboratory recently discovered that this system also demonstrates broad sensitivity to bile acids found in feces. Bile acids are an incredibly important class of molecules and are critical for dietary fat absorption, but we poorly understand how chemosensory systems use bile acid information to influence animal physiology and behavior. The goal of this research proposal is to add depth to our understanding of the mechanisms of bile acid detection by the accessory olfactory system and the spatial representation of bile acid information in the brain. Specifically, the proposed research will determine the sensitivity of mouse vomeronasal sensory neurons for fecal odorants and several relevant monomolecular bile acid ligands, which will add breadth and depth to our understanding of fecal odor and bile acid detection in the sensory periphery. Subsequently, the synaptic terminals of feces- and bile acid-sensitive neurons, which ramify in the glomerular layer of the accessory olfactory bulb, will be functionally mapped in 3-dimensions using live light sheet microscopy. Finally, the bile acid sensitivity of projection neurons, called mitral cells, that directly target the medial amygdala and bed nucleus of the stria terminalis will be evaluated, determining how bile acid information is sorted into these parallel output channels. Combined, the results will show how bile acids are encoded and prepared by neurons in the accessory olfactory system in ways that help shape animal behavior. These data will improve our understanding of brain function, and will provide a foundation for further study into chemosensory impacts on mammalian social and reproductive behaviors.