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.

抽象的 “社会气味”——有时被称为“信息素”——是婴儿喂养的关键调节剂， 繁殖和攻击。一旦被嗅觉检测到，这些信号就会起作用 调节动物的荷尔蒙状态。相反，尿液中的类固醇代谢物 成为犁鼻器官检测到的最容易理解的一类线索， 信息素的主要感觉器官之一。这种紧密结合 激素和嗅觉被认为是一种“诚实的信号”，其中有关的信息 生理状态是根据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神秘的。在老鼠身上，尽管 40 年 根据调查，自然刺激（如尿液）中主要的性别特异性犁鼻信号是 有争议或未知。最近，我的实验室开发了新技术来执行 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、内分泌操作相结合， 通过行为分析，我们确定了小鼠的第一个雌性性信息素。 在 NIH 的支持下，我们建议确定大部分或全部男性特异性尿 激活犁鼻器的线索。具体来说，我们建议（1）纯化男性特异性 配体； (2) 解析它们的化学结构，以及 (3) 识别它们的表达模式和 对两种行为的贡献，范登堡效应（青春期加速）和布鲁斯效应 效果（妊娠阻断）。这些目标有望为我们理解世界打开新的大门 性、嗅觉、激素和行为之间的关系。