Genetic Mapping of Functional Vomeronasal Circuits

7.项目摘要/摘要。 感官和内分泌系统的正常功能对人的健康和福祉至关重要。 人类。一组基本重要的先天行为，包括交配和攻击性，是 由感官反应控制的。动物进化出了专门的神经回路，将感觉输入与 内分泌系统。这些回路的功能障碍可能会导致抑郁、情绪障碍、性功能障碍 和反常行为。不同地调节内分泌反应的神经回路还没有很好的定义。 而感官体验的复杂性使研究人类的神经回路变得困难。在脊椎动物中， 先天行为，如交配仪式和领土侵犯，都是由信息素提示引起的。许多 陆生哺乳动物物种进化出了高度复杂的犁鼻系统，可以检测到 信息素，激发内分泌反应，控制行为状态。犁鼻路连接 直接进入内分泌系统并影响其输出。这些回路在很大程度上是由基因决定的。 感官输入和行为反应之间存在内在联系。类似的电路存在于 但人类可能在灵长类进化过程中被压缩成主要由主要嗅觉组成，并 包括其他感官形式。因此，小鼠犁鼻神经回路是一种理想的模型。 系统阐明感觉信息处理的神经机制、神经内分泌的机制 对先天行为的控制和感觉控制。 这项应用的目的是识别检测和处理雌性信息素的神经回路 并描述其在引诱男性性行为方面的作用。在过去，我们已经确定了两组 识别传递性身份和发情的信息素提示的犁鼻感受器 雌性小鼠的状况。我们还提纯了这些线索，它们协同作用触发了 男性。在这项研究中，我们将确定处理这些线索所传达的信息的大脑区域，并 绘制出他们之间的联系。我们将从基因上敲除已识别的受体以揭示它们的功能 对雄性骑马行为的贡献。此外，我们将从功能上审问不同的大脑区域 被信息素提示激活，以了解不同的回路成分对男性性行为的贡献 行为。这些研究有望揭示控制交配行为的高度特异的神经回路 雄性动物。这一研究成果将有助于阐明内分泌系统的调控机制 和激励状态。

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.