Olfactory receptors for semiochemical detection in the main olfactory epithelium

主嗅上皮中用于化学信息检测的嗅觉受体

• 批准号: 8960171
• 负责人: Diego Restrepo
• 金额: $ 39.48万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-07 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8960171
• 关键词: Address; Adult; Amygdaloid structure; Animal Communication; Axon; Biological Assay; Cells; Chemicals; Data; Detection; Endocrine system; Evaluation; Female; Gender; Grant; Greek; Health; Human; Image; Laboratories; Liquid substance; Major Histocompatibility Complex; Medial; Mediating; Methods; Mus; Neurons; Odors; Olfactory Cortex; Olfactory Epithelium; Olfactory Pathways; Pathway interactions; Peptides; Pheromone; Proteins; RNA; Semiochemicals; Slice; Surveys; System; Techniques; Testing; Urine; Work; base; differential expression; male; mitral cell; novel; olfactory bulb; olfactory receptor; olfactory sensory neurons; receptor; receptor expression; research study; response; sex; transcriptome sequencing; vomeronasal organ

 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.

 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 (TRPM5) 的嗅觉感觉神经元 (OSN) 子集对化学信息素（涉及动物交流的化学物质，来自希腊语）做出反应。 Semeion 表示“标志”），包括假定的信息素、来自主要组织相容性复合物 (MHC) 的肽和尿液 (2)。化学信息素并不完全由犁鼻器介导，在这项资助中，我们将测试这一假设：表达 TRPM5 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，尽管事实上人类似乎并不表达犁鼻器。器官，数据表明它们对假定的信息素和其他化学信息素有反应 (4, 5)，因此我们将进行实验寻找小鼠对化学信息素的反应。使用强大的技术，包括记录单个 OSN、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的反应，我们实现了三个具体目标： 目标 1. 检验假设小鼠 TRPM5+ OSN 中的嗅觉受体在两种性别中的表达存在差异。 目标 2：TRPM5+ OSN 是否参与低化学信息素的反应。目标 3. 检验表达 TRPM5 的 OSN 中表达的嗅觉受体对低浓度的化学信息素有反应的假设。 相关性：这项资助将检查小鼠和人类主要嗅觉上皮的嗅觉感觉神经元，以识别对化学信息素做出反应的嗅觉受体，包括假定的信息素、主要组织相容性复合物肽和从体内释放的液体。这项研究对于了解人类化学感受特别相关。 ，因为人类没有功能性犁鼻器，可以利用主要嗅觉系统来检测化学信息素 (5, 8）识别可以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，我们的研究将为介导主要嗅觉系统中的化学信息的嗅觉受体提供新的信息。