NEURAL MECHANISMS OF OLFACTORY PATTERN RECOGNITION

描述(申请人提供)：哺乳动物通过两种不同的嗅觉模式探索化学世界，称为主嗅觉系统和辅助嗅觉系统。辅助嗅觉系统(AOS)至少部分专门化地检测线索，通常被称为信息素，它调节同一物种成员之间的社会行为。虽然已经确定了许多昆虫信息素，但对老鼠和其他哺乳动物身上这些线索的性质的了解仍处于初级阶段。识别哺乳动物化学社交线索的一个有效策略是从AOS的感觉神经元记录，并使用它们的尖峰反应来指导从自然来源(如尿液)中纯化活性化合物。这种方法最近导致我们发现硫酸类固醇是雌性小鼠尿液中的主要活性来源。因为类固醇控制着哺乳动物的生理，它们的代谢物代表了一类有吸引力的社交线索，揭示了群体中其他成员的生理状态。这项申请建议进行实验，以了解更多关于哺乳动物信息素及其检测的神经生物学。(1)初步证据表明，尿液中存在许多未知的类固醇衍生物，它们激活感觉神经元；其中最主要的化合物似乎是雌激素的衍生物，可能传递有关生殖状态的信息。通过结合生化提纯、电生理学和化学分析，这些其他化合物中的一些将被鉴定。(2)不同动物的生理状态不同，尿液中硫化类固醇的含量也不同。通过记录感觉神经元对一系列不同的硫化类固醇的反应，编码同一性和浓度的机制将被阐明。这些实验还将揭示响应性神经元是否属于亲和力不同的类别。(3)对类固醇生物学的详细了解有助于对特定的硫化类固醇信息素可能的行为作用做出假设。探索警报/压力、优势和吸引力的行为实验将揭示单个化合物在组织社会行为中的确切功能。与公共健康相关：这些实验将揭示哺乳动物交流的一种主要方式的关键特性。由于它的易操纵性，探索这种模式肯定会揭示与健康和疾病中的大脑组织相关的感觉和回路功能的一般原理。

Description (provided by applicant): Mammals explore the chemical world with two distinct olfactory modalities, known as the main and accessory olfactory systems. The accessory olfactory system (AOS) is at least partially specialized to detect cues, often called pheromones, which regulate social behavior among members of the same species. While many insect pheromones have been identified, the understanding of the nature of these cues in mice and other mammals is still rudimentary. One powerful strategy for identifying mammalian chemical social cues is to record from the sensory neurons of the AOS, and use their spiking responses to guide the purification of active compounds from natural sources such as urine. This approach recently led to our identification of sulfated steroids as the predominant source of activity in female mouse urine. Because steroids control mammalian physiology, their metabolites represent an attractive class of social cue, revealing much about the physiological state of other members of the group. This application proposes experiments to learn more about mammalian pheromones and the neurobiology of their detection. (1) Preliminary evidence suggests many uncharacterized steroid derivatives present in urine activate sensory neurons; chief among these are compounds that appear to be derivatives of estrogen, potentially signaling information about reproductive state. By combining biochemical purification, electrophysiology, and chemical analysis, some of these other compounds will be identified. (2) Individual sulfated steroids in urine vary in their level depending on an animal's physiological state. By recording the responses of the sensory neurons to a concentration series of different sulfated steroids, the mechanisms for encoding identity and concentration will be elucidated. These experiments will also reveal whether responsive neurons fall into affinity distinct classes. (3) The detailed understanding of steroid biology facilitates the making of hypotheses about the likely behavioral role of particular sulfated steroid pheromones. Behavioral experiments probing alarm/stress, dominance, and attractiveness will reveal the precise function of individual compounds in organizing social behavior. PUBLIC HEALTH RELEVANCE: These experiments will reveal key properties of a major modality of mammalian communication. Because of its tractability, exploring this modality is sure to reveal general principles of sensory and circuit function with relevance to the organization of the brain in both health and disease.