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

研究小鼠附件嗅觉系统中胆汁酸的检测和处理

• 批准号: 9793995
• 负责人: Wen Mai Wong
• 金额: $ 3.33万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9793995
• 关键词: 3-Dimensional; Accessory Olfactory Bulbs; Afferent Neurons; Aggressive behavior; Amygdaloid structure; Androgens; Animal Behavior; Animals; Axon; Behavior; Behavioral; Bile Acids; Biological; Brain; Brain region; Code; Complement; Cues; Data; Detection; Dietary Fats; Electrophysiology (science); Estrogens; Excretory function; Exposure to; Feces; Female; Fishes; Foundations; Generations; Germ-Free; Glucocorticoids; Gnotobiotic; Goals; Gonadal Steroid Hormones; Health; Hormones; Human; Image; Individual; Instinct; Knowledge; Label; Laboratories; Ligands; Light; Limbic System; Logic; Mammals; Maps; Mass Spectrum Analysis; Medial; Mediating; Metabolic; Microscopy; Molecular; Mus; Neurons; Odors; Olfactory Pathways; Output; Partner in relationship; Pathway interactions; Pattern; Peripheral; Physiology; Population; Preparation; Presynaptic Terminals; Process; Reproduction; Reproductive Behavior; Research; Research Proposals; Research Training; Rodent; Role; Scientist; Sensory; Shapes; Signal Transduction; Social Behavior; Social support; Source; Specificity; Steroids; Stimulus; Structure; Structure of terminal stria nuclei of preoptic region; System; Technology; Territoriality; Training; Translating; Unspecified or Sulfate Ion Sulfates; Urine; Vertebrates; Viral; absorption; base; career; combinatorial; design; dissemination research; experimental study; improved; information processing; insight; microorganism; mitral cell; receptor; relating to nervous system; research data dissemination; response; sensory system; sex; steroid sulfate; vomeronasal organ

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.

项目总结/摘要 脊椎动物已经进化出平行的嗅觉通路来支持它们的生存和繁殖。近年来 很明显，从早期分化的鱼类到人类的脊椎动物都保留了检测环境的能力。 使用他们的嗅觉系统。在啮齿类动物中，包括小鼠，辅助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。这些神经元对分泌的类固醇很敏感， 尿中发现的雌激素、雄激素和糖皮质激素;我们的实验室最近发现， 对粪便中的胆汁酸具有广泛的敏感性。胆汁酸是一类非常重要的分子， 对于膳食脂肪吸收至关重要，但我们对化学感受系统如何利用胆汁酸信息 影响动物生理和行为。这项研究提案的目标是加深我们对 副嗅觉系统检测胆汁酸的机制及胆汁酸信息的空间表达 在大脑中。具体来说，这项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，这将增加广度和深度，我们的 了解粪便气味和胆汁酸检测的感觉周围。随后，粪便的突触末梢- 而胆汁酸敏感神经元，分支于副嗅球的肾小球层，将在功能上被 用实时光片显微镜进行三维成像。最后，投射神经元的胆汁酸敏感性， 将评估直接靶向内侧杏仁核和终纹床核的二尖瓣细胞，确定 胆汁酸信息如何被分类到这些并行输出通道中。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编码和准备，以帮助塑造动物行为的方式。这些数据 将提高我们对大脑功能的理解，并将为进一步研究化学感受器提供基础。 对哺乳动物的社会和生殖行为的影响。