IDENTITY AND NEURAL ENCODING OF SOCIAL ODORS

社会气味的身份和神经编码

• 批准号: 9513913
• 负责人: Timothy Holy
• 金额: $ 32.41万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9513913
• 关键词: Acceleration; Accessory Olfactory Bulbs; Adolescent; Adult; Afferent Neurons; Age; Aggressive behavior; Animals; Behavior; Behavioral; Charge; Chemical Structure; Code; Collaborations; Cues; Data; Detection; Deuterium; Endocrine; Esthesia; Exposure to; Family; Female; Health; Hormonal; Hormones; Hydrogen; Individual; Infant; Informatics; Investigation; Laboratories; Ligands; Mammals; Mass Spectrum Analysis; Methods; Molecular; Molecular Weight; Moods; Mus; Neurons; Neurosecretory Systems; Odors; Organ; Partner in relationship; Pathway interactions; Pattern; Perception; Pheromone; Physiological; Physiology; Pregnancy; Puberty; Regulation; Reproduction; Reproductive Behavior; Resolution; Sampling; Sensory; Sex Attractants; Sex Functioning; Signal Transduction; Smell Perception; Source; Spontaneous abortion; Steroids; Stimulus; Structure; Study models; Techniques; Ultrasonics; Uncertainty; United States National Institutes of Health; Urine; Weight; base; behavioral study; experience; feeding; insight; male; neurophysiology; relating to nervous system; response; scaffold; sex; social; tandem mass spectrometry; tool; urinary; vomeronasal organ

Abstract “Social odors”―sometimes called “pheromones”―are key regulators of infant feeding, reproduction, and aggression. Once detected by the sense of smell, these signals act to modulate the animal's hormonal status. Conversely, steroid metabolites in urine have emerged as one of the best-understood classes of cues detected by the vomeronasal organ, one of the principal sensory organs for pheromones. This tight integration between hormones and olfaction is believed to serve as an “honest signal” in which information about physiological status is inferred from metabolites of the hormones that control it. In mammals, the identity of most pheromones remains mysterious. In mice, despite 40 years of investigation, the principal sex-specific vomeronasal cues in natural stimuli like urine were controversial or unknown. Recently, my laboratory developed new techniques to perform large scale unbiased screens for the ligands that activate vomeronasal sensory neurons. Using these tools and combining them with neurophysiology, endocrine manipulations, and analysis of behavior, we have identified the first female sex pheromones for the mouse. With support from the NIH, we propose to identify most or all of the male-specific urinary cues that activate the vomeronasal organ. Specifically, we propose to (1) purify male-specific ligands; (2) solve their chemical structures, and (3) identify their pattern of expression and contributions to two behaviors, the Vandenbergh Effect (puberty acceleration) and the Bruce Effect (pregnancy block). These aims promise to open new doors in our understanding of the relationship between sex, olfaction, hormones, and behavior.

摘要 “社交气味”--有时称为“信息素”--是婴儿喂养的关键调节剂， 繁殖和侵略一旦被嗅觉检测到，这些信号就会 调节动物的荷尔蒙状态相反，尿液中的类固醇代谢物 成为犁鼻器检测到的最好理解的线索类别之一， 信息素的主要感觉器官之一。这种紧密的结合， 激素和嗅觉被认为是一种“诚实的信号”， 生理状态是从控制它的激素的代谢物推断出来的。 在哺乳动物中，大多数信息素的身份仍然是个谜。在小鼠中，尽管40年来 研究表明，尿液等自然刺激中的主要性别特异性犁鼻线索是 有争议的或未知的。最近，我的实验室开发了新的技术， 大规模无偏筛选激活犁鼻感觉神经元的配体。使用 这些工具，并将它们与神经生理学，内分泌操作， 行为分析，我们已经确定了第一个雌性性信息素的小鼠。 在美国国立卫生研究院的支持下，我们建议确定大部分或所有男性特异性尿 激活犁鼻器的信号具体而言，我们建议（1）纯化雄性特异性 配体;（2）解决其化学结构，和（3）确定其表达模式， 两种行为的贡献，范登堡效应（青春期加速）和布鲁斯 影响（妊娠阻滞）。这些目标有望为我们理解 性、嗅觉、激素和行为之间的关系。