Characterization of MS4A Chemoreceptive Function

项目摘要/摘要 当动物探索环境时，它们会遇到数以百万计的化学信号，这些信号必须是正确的 解释为识别食物和配偶并避免捕食。在哺乳动物中，这种化学物质的大部分 信息是由嗅觉系统的感觉神经元(OSNs)检测的，这些神经元表达不止一个 数千个不同的嗅觉受体(ORs)，是一种专门的化学感受器，可以感知挥发性、化学物质 香料。虽然这些受体中的许多已经在分子上定义，但它们如何发挥功能来诱导适当的 行为反应在很大程度上仍不清楚(即，老鼠如何知道逃离猫并向 一块奶酪)。这项提案概述了一系列实验，旨在利用 嗅觉系统提供的机会开始描述化学感觉的机制 信息被检测和处理以产生特定的、刻板印象的行为反应。 我们最近发现了一个由MS4A基因家族编码的新的嗅觉受体家族， 我们的初步实验表明，它们是调节对这样的刺激的先天回避反应所必需的 作为捕食者衍生的气味，对动物来说是危险的。然而，MS4A受体是如何发挥作用的 这些行为在很大程度上是未知的，这严重损害了我们对嗅觉系统如何 解释相关的感官刺激以引起适当的行为反应。开始阐明MS4A 化学感受器功能，在目标1中，我将使用诱变、电生理和钙成像来确定 MS4A如何与配体结合并发出其存在的信号。在目标2中，我将使用体外和体内的制剂 作为小鼠行为测试，以确定MS4A在传递捕食者气味存在方面的贡献 转化为适当的先天回避反应。总之，这里提出的实验将描述一种 气味受体的新家族，以及它如何发出与行为相关的气味存在的信号。大体上 总的来说，这些研究试图阐明嗅觉的基本原理，提供对哺乳动物的洞察 化学感觉，并阐明了与感官知觉相关的神经通路。

Project Summary/Abstract As animals explore their environment, they encounter millions of chemical signals that must be correctly interpreted to identify food and mates and to avoid predation. In mammals, the majority of this chemical information is detected by the sensory neurons of the olfactory system, (OSNs), which express more than one thousand distinct olfactory receptors (ORs), specialized chemoreceptors that sense volatile, chemical odorants. While many of these receptors have been molecularly defined, how they function to elicit appropriate behavioral responses remains largely unclear (i.e., how does a mouse know to run away from a cat and toward a piece of cheese). This proposal outlines a series of experiments aimed at taking advantage of the opportunities offered by the olfactory system to begin to characterize the mechanisms by which chemosensory information is detected and processed to generate specific, stereotyped behavioral responses. We have recently identified a new family of olfactory receptors encoded by the Ms4a family of genes, which our preliminary experiments suggest are required to mediate innate avoidance responses to stimuli such as predator-derived odorants that signify danger to the animal. However, how MS4A receptors function to elicit these behaviors is largely unknown, which significantly impairs our understanding of how the olfactory system interprets relevant sensory stimuli to elicit appropriate behavioral responses. To begin to elucidate MS4A chemoreceptor function, in Aim 1 I will use mutagenesis, electrophysiology, and calcium imaging to determine how MS4As bind ligands and signal their presence. In Aim 2, I will use ex vivo and in vivo preparations as well as mouse behavioral assays to determine the contribution of MS4As to transducing predator odor presence into appropriate innate avoidance responses. Together, the experiments proposed here will characterize a novel family of odorant receptor and how it signals the presence of ethologically relevant odors. Broadly speaking, these studies seek to illuminate basic principles of olfaction, provide insight into mammalian chemosensation, and shed light on the neural pathways associated with sensory perception.