Characterization of MS4A Chemoreceptive Function

项目总结/摘要 当动物探索它们的环境时，它们会遇到数百万种化学信号， 用来识别食物和配偶避免被捕食在哺乳动物中，大多数这种化学物质 信息是由嗅觉系统的感觉神经元（OSNs）检测的，OSNs表达一种以上的信息。 上千种不同的嗅觉受体（OR），专门的化学感受器， 气味剂。虽然这些受体中的许多已经被分子定义，但它们如何发挥作用以引起适当的 行为反应在很大程度上仍不清楚（即，一只老鼠怎么知道要从猫身边跑开， 一块奶酪）。该提案概述了一系列旨在利用 嗅觉系统提供的机会开始表征化学感觉的机制， 信息被检测和处理以产生特定的、定型的行为反应。 我们最近发现了由Ms 4a基因家族编码的一个新的嗅觉受体家族， 我们的初步实验表明，这是介导对刺激的先天回避反应所必需的 作为食肉动物产生的气味，对动物有危险。然而，MS 4A受体如何发挥作用， 这些行为在很大程度上是未知的，这大大削弱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MS 4A 化学感受器功能，在目标1中，我将使用诱变，电生理学和钙成像来确定 MS 4A如何结合配体并发出其存在信号。在目标2中，我将使用离体和体内制剂以及 作为小鼠行为测定以确定MS 4As对转导捕食者气味存在的贡献 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个 气味受体的新家族，以及它如何发出与行为学相关的气味的信号。广泛 这些研究试图阐明嗅觉的基本原理， 化学感觉，并阐明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.