Sensory Transduction in the Vomeronasal System

描述(申请人提供)：哺乳动物的嗅觉系统由 至少有两个功能不同的器官，即主要的嗅觉上皮和 犁鼻器(VNO)。VNO是位于吻部的一对管状结构 鼻腔末端，被认为是调节信息素、化学物质的检测 调节生殖和社会行为以及神经内分泌的信号 状态。VNO的感觉传导与大脑皮层的感觉传导不同。 嗅觉上皮，目前仍知之甚少。所描述的实验 在这项拨款中将检验这样的假设，即VNO中的感觉转导是 由与光信号转导相似的信号通路介导 在无脊椎动物身上。为了支持这一假设，我们最近发现了一种VNO- 果蝇光激活通道(DTRP)的特异性同源基因(Trp2) 高度定位于大鼠犁鼻感觉神经元的感觉微绒毛。这个 拟议的研究旨在阐明Trp2通道在 犁鼻感觉转导，以及VNO介导的行为。一个中心目标 这项工作的重点是确定激活Trp2的第二信使通路。 对果蝇的广泛研究表明，dTrp的激活位于下游 但打开dTrp通道的直接刺激不是 为人所知。我们将使用膜片钳记录技术和比率钙离子测定法 异种细胞类型的成像研究Trp2的门控反应 受体介导的磷脂酶C刺激及其直接应用 可能是第二个信使。第二个目标是确定其他组件 感官传导级联反应。 这位候选人，利曼博士，最近加入了加州大学的教职 南加州，在那里她是一名助理教授。这个ISA将极大地 通过给予应聘者急需的时间来促进她的职业发展 建立强大的研究计划，涉及各种高精尖的 技巧。候选人是一位经验丰富的电生理学家，同时也是一名 分子生物学家，提出的研究将利用她 在这些不同的技术方面的专业知识，解决生物学中的基本问题 属于犁鼻系统。

DESCRIPTION (provided by applicant): The mammalian olfactory system consists of at least two functionally distinct organs, the main olfactory epithelium and the vomeronasal organ (VNO). The VNO, a pair of tubular structures at the rostral end of the nasal cavity, is thought to mediate detection of pheromones, chemical signals that regulate reproductive and social behavior and neuroendocrine status. Sensory transduction in the VNO is distinct from that in the main olfactory epithelium, and remains poorly understood. The experiments described in this grant will test the hypothesis that sensory transduction in the VNO is mediated by a signaling pathway similar to that which mediates phototransduction in invertebrates. In support of this hypothesis, we have recently found a VNO- specific homolog (TRP2) of the Drosophila light-activated channel (dTRP) that is highly localized to sensory microvilli of rat vomeronasal sensory neurons. The proposed research is aimed at elucidating the role of the TRP2 channel in vomeronasal sensory transduction, and in VNOmediated behaviors. A central goal of this work is to identify second messenger pathways that activate TRP2. Extensive studies in Drosophila, suggest that activation of dTRP is downstream of phospholipase C, but the direct stimulus for opening dTRP channels is not known. We will use techniques of patch-clamp recording and ratiometric Ca++ imaging in heterologous cell types to study gating of TRP2 in response to receptor-mediated stimulation of phospholipase C and direct application of putative second messengers. A second goal is to identify additional components of the sensory transduction cascade. The candidate, Dr. Liman, has recently joined the faculty at the University of Southern California, where she is an assistant professor. This ISA will greatly enhance the candidate's career development by allowing her much needed time to set up a strong research program, involving a variety of sophisticated techniques. The candidate is an experienced electrophysiologist as well as a molecular biologist, and the research proposed will take advantage of her expertise in these disparate techniques to tackle basic questions in the biology of the vomeronasal system.