Genetic analysis of sexually dimorphic olfactory processing

两性嗅觉处理的遗传分析

• 批准号: 10189546
• 负责人: Chih-Ying Su
• 金额: $ 39.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10189546
• 关键词: Address; Age; Animals; Aphrodisiacs; Behavioral; Calcium; Characteristics; Complex; Copulation; Courtship; Data; Detection; Drosophila genus; Electrophysiology (science); Exhibits; Female; Food; Functional Imaging; Genes; Genetic; Goals; Hormonal; Human; Image; Individual; Insecta; Juvenile Hormones; Light; Mediating; Mental disorders; Modeling; Molecular; Names; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurons; Odorant Receptors; Odors; Olfactory Pathways; Olfactory dysfunction; Partner in relationship; Performance; Pharmacology; Pheromone; Property; Protein Isoforms; Publications; Research; Rodent; Sensory; Sex Differences; Smell Perception; Sodium Channel; Specific qualifier value; System; Testing; Woman; Work; age related; experimental study; fly; genetic analysis; genetic approach; genetic manipulation; hormone regulation; imaging approach; in vivo calcium imaging; insight; male; men; neurophysiology; reproductive; reproductive hormone; response; sex; sexual dimorphism; transcription factor

PROJECT SUMMARY/ABSTRACT The long-term goal of this project is to determine the molecular mechanisms by which sex-determining genes and reproductive hormones differentially regulate olfactory sensitivity in males and females. In humans, olfactory performance is highly dependent on age and sex; women generally outperform men in smell identification, and men are more prone to olfactory impairment as they age. Similarly, in other animal species, select groups of odorant receptor neurons (ORNs), such as those important for pheromone detection, exhibit sexually dimorphic characteristics as animals reach the age of sexual maturity. However, the mechanisms underlying sexually-dimorphic neurophysiology are poorly understood.The research outlined here takes advantage of the powerful genetic toolkit of the Drosophila olfactory system to address this complex question. In this proposal, the first aim is to determine the generality of age-dependent sensitization in courtship- promoting ORNs. The hypothesis that all courtship-promoting ORNs in males undergo age-dependent sensitization will be tested using genetic, pharmacological, and functional imaging approaches. The second aim proposes a genetic analysis of downstream effector molecules that enhance olfactory sensitivity in the courtship-promoting ORNs. Finally, the third aim will test the hypothesis that a reproductive hormone promotes age-dependent sensitization through its interaction with a male-specific transcription factor. Results from these studies are expected to yield critical mechanistic insights into how sex-determining genes and reproductive hormones jointly regulate sensory neurophysiology and olfactory processing. These insights may have implications in understanding sexually dimorphic neurophysiology and sex-specific proclivities for certain neurodegenerative diseases.

项目摘要/摘要 该项目的长期目标是确定性别决定基因 生殖激素对男性和女性的嗅觉敏感性有不同的调节作用。在人类身上， 嗅觉能力很大程度上取决于年龄和性别；女性的嗅觉能力通常比男性强 随着年龄的增长，男性更容易出现嗅觉障碍。同样，在其他动物物种中， 选择气味感受器神经元(ON)的组，例如那些对信息素检测重要的组，展示 随着动物达到性成熟年龄，性二型性特征。然而，这些机制 潜在的性-二态神经生理学被很好地理解。 利用果蝇嗅觉系统强大的遗传工具箱来解决这个复杂的问题。 在这项建议中，第一个目标是确定求爱中年龄相关的敏化的普遍性-- 提拔奥恩斯。所有促进雄性求偶的鸟都经历年龄相关的假说 将使用遗传、药理学和功能成像方法测试致敏作用。第二 AIM提出了一项对下游效应分子的遗传分析，这些分子可以增强人的嗅觉敏感度 促进求爱的奥恩斯。最后，第三个目标将检验生殖荷尔蒙的假设 通过与男性特有的转录因子相互作用，促进年龄相关的敏化。结果 从这些研究预计将产生关键的机械洞察性别决定基因和 生殖激素共同调节感觉、神经生理学和嗅觉处理。这些见解 可能 对了解性二态神经生理学和特定性别的倾向有一定的启示 神经退行性疾病。