Encoding Immune System Signals by the Mammalian Nose

通过哺乳动物鼻子编码免疫系统信号

• 批准号: 7027488
• 负责人: FRANK ZUFALL
• 金额: $ 33.46万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-15 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7027488
• 关键词: afferent nerve; animal tissue; behavioral /social science research tag; behavioral genetics; biological signal transduction; chemoreceptors; communication behavior; gene targeting; genetic polymorphism; genetically modified animals; immune system; laboratory mouse; ligands; major histocompatibility complex; molecular /cellular imaging; neural information processing; neural transmission; olfactions; peptides; protein quantitation /detection; respiratory epithelium; sex behavior; social behavior; voltage /patch clamp; vomeronasal systems

DESCRIPTION (provided by applicant): The goal of this research is to understand the molecular and cellular basis underlying mammalian chemical communication using the mouse as a model system. To reach this goal, we will take advantage of a novel functional link between the immune system and the sense of smell by which information about the immunological genotype of an individual conspecific can be converted into a chemosensory quality. This mechanism is based on the detection of a large family of peptide ligands - the MHC class I peptides - by sensory neurons in the mammalian nose. Increasing evidence indicates that the highly polymorphic genes of the major histocompatibility complex (MHC) influence mating preference and other social behaviors in mice and humans. Detection of MHC peptides provides a molecular mechanism by which this can occur. This research has three specific aims. In aim 1, we will determine how these immune system signals are encoded in spatial patterns of neuronal activity in the vomeronasal organ (VNO) and whether specific receptors are involved in this process. In aim 2, we will investigate how immune system signals are encoded in specific temporal patterns of neural activity in the VNO. And in aim 3, we will determine how immune system signals are encoded by neuronal populations in the main olfactory epithelium. This research employs a highly interdisciplinary approach involving gene-targeting methodology, analysis of cellular activity using sophisticated electrophysiological and imaging methods, and behavioral analysis in wildtype and mutant mice. The relevance of this research lies in the fact that it provides a sensory mechanism by which an individual can detect the genetic composition and compatibility of the immune system of a conspecific, information that is likely to influence a variety of social behaviors. A potential application of this reseach is in the development of olfactory sensors that can identify an individual based on genetically-determined odors.

描述（由申请人提供）：这项研究的目的是了解使用小鼠作为模型系统的哺乳动物化学交流的分子和细胞基础。为了实现这一目标，我们将利用免疫系统与嗅觉之间的新功能联系，通过这些联系可以将有关个体同种的免疫学基因型的信息转化为化学感觉质量。该机制基于通过哺乳动物鼻子中的感觉神经元检测大型肽配体（MHC I类肽）。越来越多的证据表明，主要组织相容性复合物（MHC）的高度多态基因影响小鼠和人类的交配偏好和其他社会行为。 MHC肽的检测提供了可以发生这种情况的分子机制。这项研究具有三个特定的目标。在AIM 1中，我们将确定这些免疫系统信号如何以沃马纳斯尔器官（VNO）的神经元活性的空间模式进行编码，以及是否参与了此过程。在AIM 2中，我们将研究如何在VNO中神经活动的特定时间模式中编码免疫系统信号。在AIM 3中，我们将确定免疫系统信号如何由主嗅觉上皮中的神经元种群编码。该研究采用了一种高度跨学科的方法，涉及基因靶向方法，使用复杂的电生理学和成像方法对细胞活性进行分析，以及野生型和突变小鼠中的行为分析。这项研究的相关性在于，它提供了一种感官机制，个人可以通过该机制检测出可能影响各种社会行为的特定信息的免疫系统的遗传组成和兼容性。该研究的潜在应用是在嗅觉传感器的发展中，这些传感器可以基于遗传确定的气味识别个体。