Genetic Mapping of Functional Vomeronasal Circuits

7.项目概要/摘要。 感觉和内分泌系统的正常功能对儿童的健康和福祉至关重要。 人类一组基本上重要的先天行为，包括交配和侵略， 由感官反应控制。动物已经进化出专门的神经回路，将感官输入与 内分泌系统这些回路的功能障碍可能导致抑郁、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还没有很好的定义 而感官体验的复杂性使得研究人类的神经回路变得困难。在脊椎动物中， 与生俱来的行为，如交配仪式和领土侵略是由信息素线索引起的。许多 陆栖哺乳动物进化出高度复杂的犁鼻系统， 信息素，引发内分泌反应和控制行为状态。犁鼻回路连接着 直接进入内分泌系统并影响其输出。这些电路在很大程度上是由基因决定的 在感觉输入和行为反应之间有一种内在的联系。类似的电路存在于 但在灵长类动物进化过程中可能已经被压缩，主要由主要的嗅觉组成， 包括其它感觉形态。因此，小鼠犁鼻回路是一个理想的模型 系统阐明感觉信息处理的神经机制，神经内分泌机制， 控制和感官控制的先天行为。 本申请的目的是确定检测和处理雌性信息素的神经回路 信息，并描绘其功能，引起男性性行为。在过去，我们已经确定了两套 犁鼻器的感受器，识别信息素的线索，传达性别身份和发情 雌性小鼠的状态。我们还纯化了这些线索，它们协同作用，触发了动物的交配行为。 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， 映射他们的连接。我们将从基因上敲除已鉴定的受体，以揭示它们的功能。 对雄性坐骑行为的影响此外，我们将从功能上询问不同的大脑区域， 激活的信息素线索，以了解不同的电路组件的贡献，男性性 行为这些研究有望揭示出控制交配行为的高度特异性神经回路， 雄性动物。本研究将有助于阐明内分泌系统的调控机制 和动机状态。

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.