Genetic Mapping of Functional Vomeronasal Circuits

描述（由申请人提供）：感觉和内分泌系统的正常功能对人类的健康和福祉至关重要。感觉经验对内分泌系统有直接的影响，许多经验诱发的内分泌反应是先天性的.然而，控制这些过程的神经回路还没有得到很好的理解。本研究拟以小鼠犁鼻神经回路为模型系统，探讨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，诸如交配仪式和领土侵略之类的先天行为是通过犁鼻器检测信息素线索而引起的。这些行为是稳健和刻板的，但它们的表达关键取决于对信息素的适当反应。犁鼻环路直接连接到内分泌系统并影响其输出。这些回路在很大程度上是遗传决定的，感觉输入与行为和内分泌反应之间存在内在联系，使其成为了解感觉处理和内分泌变化的感觉控制的有吸引力和易处理的回路。 这项应用的目的是确定性信息素，它们的受体和跟踪处理信息的神经回路。我们假设，男性和女性信息素引起的反应，从不同的细胞群体中的VNO。这种信息在大脑中通过感觉神经元投射的不同空间模式来表示，并允许性别歧视和不同的内分泌变化。在目标1中，我们将使用在感觉神经元中表达钙指示剂的转基因动物来识别对尿液中的特定信息素做出反应的细胞。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。我们会筛选尿液成分来化学鉴定信息素。在目标2中，我们将通过遗传标记表达性信息素受体的神经元来追踪信息流。在目标3中，我们将结合联合收割机的遗传实验与行为分析信息素控制的内分泌反应。 动物已经进化出专门的神经回路，将感觉输入与内分泌反应联系起来。感觉经验的复杂性使得研究人类内分泌反应的感觉控制变得困难。犁鼻系统在大多数脊椎动物中高度进化，专门控制内分泌系统和情绪状态。类似的回路也存在于人类中，但可能在灵长类动物进化过程中被压缩，主要由主要的嗅觉组成，并包括其他感官形式。本研究将有助于阐明内分泌系统和动机状态的控制机制，以及社会交往的处理。

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.