Genetic Mapping of Functional Vomeronasal Circuit

功能性犁鼻环路的基因图谱

• 批准号: 7740190
• 负责人: Congrong Ron Yu
• 金额: $ 37.71万
• 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 2011-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7740190
• 关键词: Accessory Olfactory Bulbs; Address; Afferent Neurons; Aggressive behavior; Alzheimer' s Disease; Animals; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Behavioral; Behavioral Assay; Brain; Calcium; Camping; Cells; Chemicals; Chromosome Mapping; Cues; Defect; Detection; Diagnostic; Discrimination; Female; Gender; Genetic; Genetic Suppression; Goals; Health; Image; Imaging Techniques; Individual; Instinct; Knowledge; Label; LacZ Genes; Light; Link; Maps; Mental Depression; Mental disorders; Methods; Molecular Biology; Monitor; Mus; Neurologic; Neurons; Output; Parkinson Disease; Partner in relationship; Pathway interactions; Pattern; Perception; Pheromone; Pheromone Receptors; Population; Proteins; Receptor Gene; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Ritual compulsion; Sampling; Schizophrenia; Sensory; Sensory Process; Stereotyping; System; Testing; Tetanus Toxin; Tetracyclines; Therapeutic; Transgenic Animals; Urine; Vertebrates; Vomeronasal Systems; base; calcium indicator; information processing; insight; inward rectifier potassium channel; male; neural circuit; programs; promoter; receptor; relating to nervous system; reproductive; research study; response; selective expression; sensory mechanism; sensory system; social; vomeronasal organ

The major goal of this proposal is to understand the mechanisms and the general principles involved in sensory informationprocessing. 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.

这项建议的主要目标是了解以下机制和一般原则 感官信息处理。感官系统的正常功能对我们的健康和健康至关重要 是存在的。许多神经和精神疾病，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。感官缺陷是 也是帕金森氏症和阿尔茨海默氏症的最早迹象。对感觉系统的研究将使 让我们了解大脑是如何运作的，并帮助我们将这些知识用于诊断和治疗 申请。为了实现这一目标，人们必须研究检测和整合感觉输入的神经电路 并产生不同的行为输出。脊椎动物的先天行为，如交配仪式和领地 攻击在很大程度上是通过犁鼻器官检测到信息素线索而引发的。这些 行为是健壮的和刻板的，它们的表达关键取决于对 信息素。信息素检测所涉及的神经回路在很大程度上是由基因决定的。的确有 感觉输入和犁鼻系统中的行为反应之间的内在联系，使其成为 吸引人的和易于处理的电路，以了解感觉处理。 在这项研究中，我们检验了感觉信息以激活模式编码的假设 感觉细胞中不同的信息素。这一信息在大脑中进一步由 来自这些神经元的地形图投射，使动物能够区分性别、压力和社会和 其他个体的生殖状况。我们将首先开发表达钙的转基因动物 感觉神经元中的指示器，用于识别对特定信息素做出反应的细胞。组合荧光 成像，小鼠遗传学和分子生物学，然后我们将确定信息素受体基因这些 细胞表达。第三，我们将通过绘制犁鼻通路与基因的图谱来追踪信息流 贴标签实验。最后，我们将在基因上灭活犁鼻中的神经元亚群。 阐明它们对信息素感知的功能贡献的途径。这一功能映射 犁鼻回路将提供对感觉系统如何检测、解析和整合的洞察力 引出特定行为的信息。