Mammalian bile acid detection, processing, and impact on social behavior

哺乳动物胆汁酸检测、处理及其对社会行为的影响

• 批准号: 10222213
• 负责人: Julian P Meeks
• 金额: $ 42.57万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222213
• 关键词: Accessory Olfactory Bulbs; Afferent Neurons; Animals; Anxiety; Area; Behavior; Behavior assessment; Behavioral; Behavioral Paradigm; Bile Acids; Biochemical; Biological; Brain; Brain imaging; Brain region; Calcium; Cells; Chemicals; Cholesterol; Chromosome Mapping; Complement; Coprophagia; Coupled; Cues; Data; Detection; Diet; Dietary Fats; Digestion; Disease; Environment; Esthesia; Evolution; Family; Fatty acid glycerol esters; Feces; Foundations; G-Protein-Coupled Receptors; GPBAR1 gene; Gene Expression; Glucocorticoids; Goals; Health; Human; Image; Imaging Techniques; Immediate-Early Genes; In Situ Hybridization; Individual; Kairomones; Knowledge; Laboratories; Learning; Life; Link; Liver; Mammals; Maternal Behavior; Measures; Metabolic; Metabolism; Methods; Moods; Mus; Neurons; Nose; Olfactory Pathways; Pattern; Peripheral; Pheromone; Physiology; Population; Positioning Attribute; Process; Production; Property; Reproduction; Reproductive Behavior; Research; Research Proposals; Rodent; Rodent Control; Role; Sensory; Sensory Receptors; Signal Transduction; Social Behavior; Source; Steroids; Sulfate; Techniques; Testing; Urine; Vitamins; absorption; base; behavioral response; brain pathway; experimental study; gut microbes; improved; information processing; insight; microorganism; mitral cell; neural circuit; neuromechanism; next generation; receptor; reproductive; sensory system; sex; social anxiety; transcriptome; transcriptome sequencing; urinary; vomeronasal organ

Project Summary/Abstract The overall goal of this research plan is to improve understanding about mammalian bile acid chemosignaling through the accessory olfactory system (AOS). Bile acids – well known regulators of fat digestion and metabolism – also serve as external chemosignals for the AOS. In most mammals, the AOS directly influences brain regions that control anxiety and social behaviors, and understanding this brain pathway is likely to provide insights into mammalian sexual/reproductive drive, social anxiety, and moods. New knowledge about AOS function may be utilized to help control rodent populations, including those that harbor harmful microorganisms. The mechanisms of peripheral bile acid sensation, the mechanisms of bile acid information processing in the brain, and the behavioral impacts of bile acids are currently unknown. The proposed research will combine new calcium imaging techniques with transcriptome analysis to identify the peripheral AOS receptor(s) sensitive to bile acids. Other proposed experiments will investigate network properties in accessory olfactory bulb (AOB), where bile acid and other steroid information is integrated. Finally, behavioral assessment will be coupled to brain-wide immediate early gene mapping to determine the overall impacts of bile acid chemosensation on brain activity and behavior. The proposed research will investigate these topics in order to improve understanding of this important class of mammalian chemosignals. The results of the proposed experiments will ultimately benefit human health by linking mammalian gut physiology to brain function.

项目总结/摘要 这项研究计划的总体目标是提高对哺乳动物胆汁酸化学信号的理解 辅助嗅觉系统（AOS）胆汁酸-众所周知的脂肪消化调节剂， 代谢-也作为外部化学信号的AOS。在大多数哺乳动物中，AOS直接影响 控制焦虑和社会行为的大脑区域，了解这种大脑通路可能会 提供对哺乳动物性/生殖驱动力，社交焦虑和情绪的见解。新认识 AOS功能可用于帮助控制啮齿动物种群，包括那些具有有害生物的啮齿动物种群。 微生物的外周胆汁酸感觉的机制，胆汁酸信息的机制 胆汁酸在大脑中的处理，以及胆汁酸的行为影响目前尚不清楚。拟议 研究将联合收割机新的钙成像技术与转录组分析相结合， 对胆汁酸敏感的AOS受体。其他拟议的实验将调查网络属性， 副嗅球（AOB），胆汁酸和其他类固醇信息的整合。最后，行为 评估将与全脑立即早期基因图谱相结合，以确定 胆汁酸化学感觉对大脑活动和行为的影响。拟议的研究将调查这些主题， 以提高对这类重要的哺乳动物化学信号的理解。的结果 拟议中的实验将通过将哺乳动物的肠道生理学与大脑联系起来， 功能