Odorant Receptors and Functional Mapping

描述(由申请人提供)：嗅觉系统正在成为一种 用于研究神经元连接和信息处理的吸引人的模型 哺乳动物的大脑。这个系统代表了关于分子刺激的信息，在 部分，作为大脑嗅球激活的空间模式。这个 这些气味表现的分子基础正在通过以下研究得到阐明 嗅觉功能的遗传基础。在哺乳动物中，嗅觉是由一种 气味受体大家族在化学感觉神经元中表达。海流 假设气味感受器在嗅觉中有两个不同的作用 功能：调节气味反应，影响轴突连接 到嗅球的投射。这一想法提出了重要的问题，如 什么信息被映射到大脑表面。这些活动的目标是 研究的目的是要开始阐明这两个角色之间的关系。这个 第一个目标是确定ORS(配体结合)的不同功能 和轴突引导)可以分开。这将通过创造小鼠品系来实现 在已定义的内源性气味受体基因座上有针对性的基因突变， 检测表达荧光标记神经元的气味特异性 定义受体，并将这些数据与观察到的轴突路径相关联 活体内的行为。第二个目标是确定气味特异性或 受体序列与神经元投射的位置相关 是由一组气味受体决定的，这些气味受体是由一个确定的遗传位点表达的。臭味剂 将测量反应曲线，并对表达的受体进行测序 投射到嗅球局部区域的传入由 基因标记神经元的投射。解决这些问题提供了一个 了解哺乳动物神经系统如何表现的第一步 化学信息。基因打靶与光学成像技术的结合 神经元活动为研究信息编码提供了强有力的工具 在哺乳动物嗅觉系统中。靶向表达的一般方法 外源蛋白质(例如，遗传编码的光学指示物)的定义 神经元群体可以提供新的方法来监测神经元的活动。 完整的神经元回路。

DESCRIPTION (provided by applicant): The olfactory system is emerging as an attractive model for studying neuronal wiring and information processing in the mammalian brain. This system represents information about molecular stimuli, in part, as spatial patterns of activation in the olfactory bulb of the brain. The molecular basis for these odor representations is being elucidated by studies on the genetic basis of olfactory function. In mammals, olfaction is mediated by a large family of odorant receptors expressed in chemosensory neurons. The current hypothesis is that odorant receptors have two distinct roles in olfactory function: mediating odorant responsiveness and influencing the wiring of axonal projections to the olfactory bulb. This idea raises important questions as to what information is mapped onto the surface of the brain. The objective of these studies is to begin to elucidate the relationship between these two roles. The first aim is to determine whether the distinct functions of ORs (ligand binding and axon guidance) can be separated. This will be done by creating mouse strains with targeted genetic mutations in a defined endogenous odorant receptor locus, assaying the odorant specificity of fluorescently tagged neurons expressing defined receptors, and correlating these data with observed axon pathfinding behavior in vivo. The second aim is to determine whether odorant specificity or receptor sequence correlate with the location of neuronal projections dictated by a set of odorant receptors expressed from a defined genetic locus. Odorant response profiles will be measured, and expressed receptors sequenced from afferents projecting to local regions of the olfactory bulb defined by the projections of genetically tagged neurons. Addressing these issues provides a first step towards understanding how the mammalian nervous system represents chemical information. The combination of gene targeting and optical imaging of neuronal activity provides powerful tools for investigating information coding in the mammalian olfactory system. The general approach of targeting expression of exogenous proteins (e.g., genetically encoded optical indicators) to defined neuronal populations could provide new methods to monitor neuronal activity in intact neuronal circuits.