Genetic Mapping of Functional Vomeronasal Circuit

功能性犁鼻环路的基因图谱

• 批准号: 7020272
• 负责人: Congrong Ron Yu
• 金额: $ 39.75万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7020272
• 关键词: calcium indicator; chemoreceptors; fluorescent dye /probe; gene induction /repression; genetic mapping; genetic promoter element; genetically modified animals; laboratory mouse; neural information processing; neurogenetics; pheromone; sensory discrimination; vomeronasal systems

DESCRIPTION (provided by applicant): The major goal of this proposal is to understand the mechanisms and the general principles involved in sensory information processing. The proper function of the sensory systems is crucial to our health and well being. Numerous neurological and psychiatric disorders, such as schizophrenia, autism, attention deficit hyperactivity disorder (ADHD) and depression, all manifest defects in sensory responses. Sensory deficit is also the earliest sign of Parkinson's and Alzheimer's diseases. The study of the sensory systems will enable us to understand how the brain functions and help us to use this knowledge for diagnostic and therapeutic applications. To achieve this goal, one must study the neural circuitry that detects and integrates sensory input and elicits distinct behavioral output. In vertebrates, innate behaviors such as mating rituals and territorial aggression are largely elicited by the detection of pheromone cues through the vomeronasal organ. These behaviors are robust and stereotyped and their expression critically depends on the correct identification of pheromones. The neural circuits involved in pheromone detection are largely genetically determined. There is an intrinsic link between sensory input and behavior responses in the vomeronasal system, making it an attractive and tractable circuitry to understand sensory processing. In this study, we test the hypothesis that sensory information is encoded in the pattern of activation by different pheromones in the sensory cells. This information is further represented in the brain by the topographic projection from these neurons to allow an animal to discriminate gender, strain and the social and reproductive status of other individuals. We will first develop transgenic animals expressing calcium indicators in the sensory neurons to identify cells that respond to specific pheromones. Combining fluorescent imaging, mouse genetics and molecular biology, we will then identify the pheromone receptor gene these cells express. Third, we will trace the information flow by mapping the vomeronasal pathway with genetic labeling experiments. Finally, we will genetically inactivate subpopulations of neurons in the vomeronasal pathway to elucidate their functional contribution to pheromone perception. This functional mapping of the vomeronasal circuit will provide insight into how the sensory system detects, parses and integrates information to elicit specific behaviors.

描述（由申请人提供）：该提案的主要目标是了解感官信息处理中涉及的机制和一般原则。 感觉系统的正确功能对于我们的健康和福祉至关重要。 许多神经系统和精神疾病，例如精神分裂症，自闭症，注意力缺陷多动症（ADHD）和抑郁症，都表现出感觉反应的缺陷。 感官赤字也是帕金森氏症和阿尔茨海默氏症疾病的最早迹象。 对感官系统的研究将使我们能够了解大脑的功能并帮助我们将这些知识用于诊断和治疗应用。 为了实现这一目标，必须研究检测和整合感觉输入并引起独特的行为输出的神经回路。 在脊椎动物中，通过沃梅隆斯器官检测信息素提示，在很大程度上引起了天生的行为，例如交配仪式和领土侵略。 这些行为坚固且刻板印象，它们的表达严重取决于信息素的正确识别。 信息素检测涉及的神经回路在很大程度上是遗传确定的。 在沃马纳纳纳斯系统中的感觉输入和行为响应之间存在着内在的联系，使其成为一种吸引人且可拖动的电路，以了解感觉处理。 在这项研究中，我们检验了一个假说，即感觉信息是通过感觉细胞中不同信息素激活模式编码的。 这些信息通过这些神经元的地形投影进一步代表了大脑，以允许动物区分其他人的性别，压力以及社会和生殖状况。 我们将首先开发出表达感觉神经元中钙指标的转基因动物，以鉴定对特定信息素反应的细胞。 结合荧光成像，小鼠遗传学和分子生物学，我们将确定这些细胞表达的信息素受体基因。 第三，我们将通过遗传标记实验映射呕吐途径来追踪信息流。 最后，我们将在综合上灭活呕吐途径中神经元的亚群，以阐明其对信息素感知的功能贡献。 Vomeronasal电路的功能映射将提供有关感觉系统如何检测，解析和集成信息以引起特定行为的洞察力。