Genetic Mapping of Functional Vomeronasal Circuits

功能性犁鼻回路的基因图谱

基本信息

批准号：
8461192
负责人：
Congrong Ron Yu
金额：
$ 32.1万
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：
2006
资助国家：
美国
起止时间：
2006-01-10 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8461192
关键词：
Adopted Afferent Neurons Aggressive behavior Animals Behavior Behavioral Behavioral Assay Biological Models Brain Calcium Cells Chemical Structure Chemicals Chromosome Mapping Cognitive deficits Cues Defect Detection Diagnostic Emotional Endocrine Endocrine system Estrus Evolution Family Female Genetic Genetically Engineered Mouse Goals Health High Pressure Liquid Chromatography Human Hypothalamic structure Image Individual Instinct Knowledge Label Link Logic Maps Mediating Mental disorders Methodology Modality Molecular Biology Motivation Mus Nature Neural Pathways Neurons Neurosecretory Systems Output Partner in relationship Pattern Perception Pheromone Pheromone Receptors Population Primates Process Proteins Publishing Receptor Gene Reproductive Behavior Reverse Transcriptase Polymerase Chain Reaction Ritual compulsion Sensory Sensory Process Sex Attractants Sex Discrimination Sexual Maturation Signal Transduction Stereotyping Stimulus System Testing Therapeutic Transgenic Animals Transgenic Mice Urine Vertebrates Vomeronasal Systems Well in self base calcium indicator experience information processing innovation insight liquid chromatography mass spectrometry male neural circuit neuromechanism novel novel strategies receptor research study response sensor sensory mechanism sensory system sex social social communication vomeronasal organ

项目摘要

DESCRIPTION (provided by applicant): The proper functioning of the sensory and endocrine systems is essential for the health and well being of human beings. Sensory experiences often have direct influence on endocrine systems and many experience- induced endocrine responses are innate. However, the neural circuitry that controls these processes is not well understood. In the proposed project, we will study the mouse vomeronasal circuitry as a model system to elucidate the neural mechanism of sensory information processing and mechanism of sensory control of endocrine function. In vertebrates, innate behaviors such as mating rituals and territorial aggression are elicited by the detection of pheromone cues through the vomeronasal organ. These behaviors are robust and stereotyped, but their expression critically depends on the proper response to pheromones. The vomeronasal circuit connects directly to the endocrine systems and influences their output. These circuits are largely genetically determined and there is an intrinsic link between sensory input and the behavior and endocrine responses, making it an attractive and tractable circuitry to understand sensory processing and sensory control of endocrine changes. The objective of this application is to identify the sex pheromones, their receptors and trace the neural circuitry processing the information. We hypothesize that male and female pheromones elicit responses from distinct populations of cells in the VNO. This information is represented in the brain by the distinct spatial patterns of the sensory neuron projection and allows sex discrimination and differential endocrine changes in response. In Aim 1, we will use transgenic animals expressing calcium indicators in the sensory neurons to identify cells that respond to specific pheromones in urine. Combining fluorescent imaging, mouse genetics and molecular biology, we will identify the pheromone receptor gene expressed by these cells. We will screen urine fractions to chemically identify the pheromones. In Aim 2, we will trace the information flow by genetically labeling the neurons expressing the sex pheromone receptors. In Aim 3, we will combine genetic experiments with behavioral assays to analyze pheromone control of endocrine responses. Animals have evolved specialized neural circuitry that links sensory input to endocrine responses. The complexity of sensory experiences makes it difficult to study sensory control of endocrine response in humans. The vomeronasal system is highly evolved in most vertebrate species and is specialized in controlling endocrine system and emotional states. Similar circuits exist in humans but may have been compacted during primate evolution to consist of mostly the main olfactory, and to include other sensory modalities. Insight gained from this study will help to elucidate control mechanism of endocrine systems and motivational states, as well as the processing of social communication.

描述（由申请人提供）：感觉和内分泌系统的正确功能对于人类的健康和福祉至关重要。感官体验通常对内分泌系统有直接影响，许多经验引起的内分泌反应是先天的。但是，控制这些过程的神经回路尚不清楚。在拟议的项目中，我们将研究小鼠呕吐电路作为模型系统，以阐明感觉信息处理的神经机制和内分泌功能的感觉控制机制。在脊椎动物中，通过vomeronasal器官检测信息素提示，从而引发了诸如交配仪式和领土侵略之类的先天行为。这些行为是牢固的，刻板印象，但是它们的表达在很大程度上取决于对信息素的适当反应。 Vomeronasal电路直接连接到内分泌系统并影响其输出。这些电路在很大程度上是遗传确定的，并且在感觉输入与行为和内分泌反应之间存在固有的联系，使其成为一种有吸引力且可拖动的电路，以了解内分泌变化的感觉处理和感觉控制。该应用的目的是识别性信息素，其受体并追踪处理信息的神经回路。我们假设男性和女性信息素会引起VNO中不同细胞种群的反应。该信息在大脑中通过感觉神经元投影的不同空间模式表示，并允许性别歧视和差异内分泌变化。在AIM 1中，我们将使用表达感觉神经元中钙指标的转基因动物来鉴定对尿液中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。我们将筛选尿液分数以化学识别信息素。在AIM 2中，我们将通过对表达性信息素受体的神经元进行基因标记来追踪信息流。在AIM 3中，我们将结合遗传实验与行为测定，以分析信息素的内分泌反应的控制。动物已经进化了专门的神经回路，将感觉输入与内分泌反应联系起来。感觉经历的复杂性使研究人类内分泌反应的感觉控制很难。在大多数脊椎动物物种中，Vomeronasal系统都在高度发展，并且专门用于控制内分泌系统和情绪状态。人类存在类似的电路，但在灵长类动物的演化过程中可能已经压实，主要由主要的嗅觉组成，并包括其他感觉方式。从这项研究中获得的洞察力将有助于阐明内分泌系统和动机状态的控制机制，以及社会交流的处理。