Genetic analysis of sexually dimorphic olfactory processing

项目总结/摘要 该项目的长期目标是确定性别决定基因的分子机制， 生殖激素对雄性和雌性的嗅觉敏感性有不同的调节作用。在人类中， 嗅觉表现高度依赖于年龄和性别;女性在嗅觉方面通常优于男性 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， 选择组气味受体神经元（ORN），如那些重要的信息素检测，表现出 当动物达到性成熟的年龄时，性的二型特征。然而，机制 潜在的性二态神经生理学知之甚少。这里概述的研究 果蝇嗅觉系统强大的遗传工具包的优势来解决这个复杂的问题。 在这个建议中，第一个目的是确定求爱中年龄依赖敏感化的普遍性- 促进ORN。假设所有的求偶促进ORN在男性经历年龄依赖性 将使用遗传学、药理学和功能成像方法测试致敏性。第二 aim提出了一种增强嗅觉敏感性的下游效应分子的遗传分析， 促进求爱的ORN最后，第三个目标将检验生殖激素 通过与男性特异性转录因子的相互作用促进年龄依赖性致敏。结果 从这些研究中，有望对性别决定基因和 生殖激素共同调节感觉神经生理学和嗅觉处理。这些见解 可以 对理解某些人的性二态神经生理学和性别特异性倾向有意义。 神经退行性疾病

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.