Genetic Mapping of Functional Vomeronasal Circuits

功能性犁鼻回路的基因图谱

• 批准号: 9243539
• 负责人: Congrong Ron Yu
• 金额: $ 35.06万
• 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 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9243539
• 关键词: Accessory Olfactory Bulbs; Adopted; Aggressive behavior; Animals; Area; Behavior; Behavior Control; Behavioral; Behavioral Assay; Biological Models; Brain; Brain region; Chemicals; Chromosome Mapping; Cognitive deficits; Cues; Defect; Detection; Diagnostic; Endocrine; Endocrine system; Estrus; Evolution; Family; Female; Functional disorder; Funding; Genetic; Goals; Health; Human; Hypothalamic structure; Immediate-Early Genes; Individual; Instinct; Knock-out; Knowledge; Label; Lead; Learning; Link; Location; Logic; Maps; Mediating; Mental Depression; Mental disorders; Modality; Mood Disorders; Motivation; Mus; Neurons; Neurosecretory Systems; Output; Partner in relationship; Pathway interactions; Pattern; Perception; Pheromone; Play; Population; Primates; Process; Publishing; Reproductive Behavior; Ritual compulsion; Role; Sensory; Sex Attractants; Sex Behavior; Sexual Dysfunction; Sexual Maturation; Signal Transduction; Specificity; System; Testing; Therapeutic; Transgenic Mice; Transgenic Organisms; Urine; Vertebrates; Vomeronasal Systems; Well in self; abstracting; behavioral response; brain cell; experience; information processing; innovation; insight; knockout gene; male; mating behavior; neural circuit; neuromechanism; novel strategies; optogenetics; public health relevance; receptor; research study; response; sensory input; sensory mechanism; sensory system; social; social communication; tool; urinary; vomeronasal organ

7. Project Summary/Abstract. The proper function of the sensory and endocrine systems is essential for the health and well being of human beings. A set of fundamentally important innate behaviors, including mating and aggression, are controlled by sensory responses. Animals have evolved specialized neural circuitry that links sensory input to endocrine systems. Dysfunction in these circuits may lead to depression, mood disorders, sexual dysfunction and aberrant behaviors. The neural circuits that differentially regulate endocrine responses are not well defined and the complexity of sensory experiences makes it difficult to study the circuits in humans. In vertebrates, innate behaviors such as mating rituals and territorial aggression are elicited by pheromone cues. Many terrestrial mammalian species have evolved highly sophisticated vomeronasal systems that detect pheromones, elicit endocrine responses and control behavioral states. 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 responses. 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. The mouse vomeronasal circuitry, therefore, serves as an ideal model system to elucidate the neural mechanism of sensory information processing, mechanism of neuroendocrine control and sensory control of innate behaviors. The objective of this application is to identify the neural circuitry that detect and process female pheromone information and delineate its function in eliciting male sexual behaviors. In the past, we have identified two sets of vomeronasal receptors that recognize pheromones cues that convey the sexual identity and the estrous status of female mice. We also purified these cues, which act synergistically to trigger mounting behavior in the males. In this study, we will identify the brain regions that process information conveyed by these cues and map their connections. We will genetically knock out the identified receptors to reveal their functional contribution to male mounting behavior. Moreover, we will functionally interrogate different brain regions activated by the pheromone cues to understand the contribution of distinct circuit components to male sexual behavior. These studies are expected to reveal highly specific neural circuits that control mating behaviors in the male animals. Insight gained from this study will help to elucidate control mechanism of endocrine systems and motivational states.

7。项目摘要/摘要。 感觉和内分泌系统的适当功能对于健康和福祉至关重要 人类。一组根本重要的先天行为，包括交配和侵略，是 由感觉响应控制。动物已经进化了专门的神经回路，将感觉输入与 内分泌系统。这些电路中的功能障碍可能导致抑郁症，情绪障碍，性功能障碍 和异常行为。差异调节内分泌反应的神经回路没有很好地定义 感官体验的复杂性使研究人类的电路很难。在脊椎动物中， 信息素提示引起了天生的行为，例如交配仪式和领土侵略。许多 陆生哺乳动物物种已进化出高度复杂的呕吐系统，以检测 信息素，引起内分泌反应和控制行为状态。 Vomeronasal电路连接 直接进入内分泌系统并影响其产量。这些电路在很大程度上是遗传确定的 感觉输入与行为响应之间存在固有的联系。类似的电路 人类，但可能在灵长类动物演变中被压实，主要由主要嗅觉组成，而 包括其他感官方式。因此，小鼠的呕吐电路是理想的模型 阐明感觉信息处理的神经机制，神经内分泌的机制 控制和感官控制先天行为。 该应用的目的是确定检测和处理女性信息素的神经回路 信息并描述其在引起男性性行为方面的功能。过去，我们确定了两套 识别传达性认同和发情的信息素提示的伏美纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳纳斯受体的 雌鼠的状态。我们还纯化了这些提示，这些提示是协同作用以触发安装行为的 男性。在这项研究中，我们将确定处理这些线索传达的信息的大脑区域以及 映射他们的连接。我们将基因敲除鉴定的受体以揭示其功能 对男性安装行为的贡献。此外，我们将在功能上询问不同的大脑区域 通过信息素提示激活，以了解不同的电路成分对男性性的贡献 行为。预计这些研究将揭示高度特定的神经回路，以控制交配行为 雄性动物。从这项研究中获得的洞察力将有助于阐明内分泌系统的控制机制 和动机状态。