Genetic Mapping of Functional Vomeronasal Circuit

本建议的主要目标是了解所涉及的机制和一般原则， 感觉信息处理感觉系统的正常功能对我们的健康至关重要 存在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 也是帕金森氏症和老年痴呆症的最早征兆。对感觉系统的研究 我们了解大脑的功能，并帮助我们使用这些知识进行诊断和治疗 应用.为了达到这个目标，人们必须研究检测和整合感觉输入的神经回路 并消除不同的行为输出。在脊椎动物中，天生的行为，如交配仪式和领土 攻击性很大程度上是通过犁鼻器检测信息素线索而引起的。这些 行为是稳健和刻板的，它们的表达关键取决于正确识别 费洛蒙参与信息素检测的神经回路在很大程度上是由基因决定的。有 犁鼻系统中感觉输入和行为反应之间的内在联系，使其成为一种 有吸引力和易于处理的电路来理解感觉处理。 在这项研究中，我们测试的假设，感觉信息编码的激活模式， 不同的信息素。这些信息在大脑中进一步表现为 从这些神经元的地形投射，使动物能够区分性别，应变和社会， 其他个体的生殖状态。我们将首先培育出表达钙离子的转基因动物 感觉神经元中的指示物来识别对特定信息素做出反应的细胞。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的遗传图谱来追踪信息流。 标签实验最后，我们将从遗传学上研究犁鼻神经元的亚群， 途径，以阐明其功能的信息素感知的贡献。这个函数映射 犁鼻回路将提供对感觉系统如何检测、解析和整合的深入了解 信息来引出特定的行为。

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.