Olfactory receptors for semiochemical detection in the main olfactory epithelium

 描述（由申请人提供）：我们实验室最近的工作表明，在小鼠中，表达瞬时受体电位通道M5（TRPM 5）的嗅觉感觉神经元（OSN）的一个子集对化学信息素（参与动物交流的化学物质，来自希腊语semeion，意为“信号”）产生反应，包括推定的信息素、来自主要组织相容性复合体（MHC）的肽和尿液（2）。因此，对推定的信息素和其他信息素的反应并不完全由犁鼻器介导。在这项研究中，我们将测试这一假设，即表达TRPM 5的OSN子集使用特定的嗅觉受体子集对化学信息素做出反应。重要的是，尽管事实上，人类似乎不表达犁鼻器，数据表明，他们响应推定的信息素和其他化学信息素（4，5）。因此，我们将进行实验，寻找小鼠和人类对化学信息素的反应。使用强大的技术，包括从单个OSN记录，使用RNA-Seq评估这些神经元中的嗅觉受体表达，以及记录特定嗅觉受体对大量化学信息素和气味剂的反应，我们提出了三个具体目标：目标1。测试小鼠TRPM 5 + OSN中嗅觉受体在两种性别中差异表达的假设。 目标2. TRPM 5 + OSNs是否参与人类和小鼠对低浓度化学信息素的反应？ 目标3.测试在TRPM 5表达OSN中表达的嗅觉受体对低浓度的化学信息素作出反应的假设。 相关性：这项拨款将检查小鼠和人类主要嗅觉上皮的嗅觉感觉神经元，以确定嗅觉受体，这些嗅觉受体对包括推定的信息素，主要组织相容性复合物肽和从体内释放的液体在内的信息素有反应。这项研究是特别相关的，以了解人类化学感受，因为人类没有一个功能犁鼻器官，并可能利用主要的嗅觉系统检测化学信息素（5，8）。识别能够操纵人类激素系统的挥发性分子将是控制人类健康的重要非侵入性方法。我们的研究将提供新的信息，嗅觉受体介导的信息化学传感的主要嗅觉系统。

 DESCRIPTION (provided by applicant): Recent work from our laboratory shows that in mice a subset of the olfactory sensory neurons (OSNs) that express the transient receptor potential channel M5 (TRPM5) respond to semiochemicals (chemicals involved in animal communication, from the Greek semeion for ``sign'') including putative pheromones, peptides from the major histocompatibility complex (MHC) and urine (2). Therefore, the response to putative pheromones and other semiochemicals is not mediated exclusively by the vomeronasal organ. In this grant we will test the hypothesis that this subset of OSNs expressing TRPM5 respond to semiochemicals using a specific subset of olfactory receptors. Importantly, despite the fact that humans do not appear to express a vomeronasal organ, data suggest that they respond to putative pheromones and other semiochemicals (4, 5). Therefore we will perform experiments searching for responses to semiochemicals in mice and humans. Using strong techniques involving recording from single OSNs, evaluation of olfactory receptor expression in these neurons using RNA-Seq, and recording responses of specific olfactory receptors to large numbers of semiochemicals and odorants we propose three specific aims: Aim 1. Test the hypothesis that olfactory receptors in mouse TRPM5+ OSNs are differentially expressed in the two genders. Aim 2. Are TRPM5+ OSNs involved in responses to semiochemicals at low concentrations in both human and mouse? Aim 3. Test the hypothesis that olfactory receptors expressed in TRPM5-expressing OSNs respond to semiochemicals at low concentrations. RELEVANCE: This grant will examine olfactory sensory neurons from the main olfactory epithelium of mice and humans to identify olfactory receptors that respond to semiochemicals including putative pheromones, major histocompatibility complex peptides and liquids released from the body. This study is particularly relevant to understand human chemoreception, as humans do not have a functional vomeronasal organ and may utilize the main olfactory system for detection of semiochemicals (5, 8). Identifying volatile molecules that can manipulate the hormonal system of humans would be an important non-invasive method for control of human health. Our studies will provide novel information on olfactory receptors mediating semiochemical sensing in the main olfactory system.