Genetic Mapping of Functional Vomeronasal Circuit

功能性犁鼻环路的基因图谱

基本信息

批准号：
7844591
负责人：
Congrong Ron Yu
金额：
$ 2.86万
依托单位：
STOWERS INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7844591
关键词：
Accessory Olfactory Bulbs Address Afferent Neurons Aggressive behavior Alzheimer&apos 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 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 depression 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

项目摘要

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.

该提案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，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。感觉缺陷是也是帕金森病和阿尔茨海默病的最早迹象。对感觉系统的研究将使我们了解大脑如何运作并帮助我们利用这些知识进行诊断和治疗应用程序。为了实现这一目标，必须研究检测和整合感觉输入的神经回路并引发独特的行为输出。在脊椎动物中，诸如交配仪式和领地意识等先天行为攻击性很大程度上是由犁鼻器官检测信息素线索引起的。这些行为是鲁棒的和刻板的，它们的表达关键取决于对信息素。信息素检测涉及的神经回路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，使其成为有吸引力且易于处理的电路来理解感觉处理。在这项研究中，我们测试了以下假设：感觉信息以激活模式编码感觉细胞中存在不同的信息素。该信息在大脑中进一步由这些神经元的地形投影使动物能够区分性别、应变以及社会和社会地位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标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，然后我们将识别这些信息素受体基因细胞表达。第三，我们将通过用遗传图谱绘制犁鼻通路来追踪信息流。标记实验。最后，我们将从基因上灭活犁鼻神经元亚群阐明它们对信息素感知的功能贡献的途径。这个功能映射犁鼻环路将深入了解感觉系统如何检测、解析和整合引发特定行为的信息。