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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：
7850288
负责人：
Congrong Ron Yu
金额：
$ 23万
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：
2009-07-17 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7850288
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.

本提案的主要目标是了解所涉及的机制和一般原则