Odorant Receptors and Functional Mapping

描述（由申请人提供）：嗅觉系统正在成为一种 有吸引力的模型，用于研究神经元布线和信息处理， 哺乳动物的大脑这个系统代表了分子刺激的信息， 部分，作为大脑嗅球激活的空间模式。的 这些气味表征的分子基础正在通过以下研究来阐明： 嗅觉功能的遗传基础在哺乳动物中，嗅觉是由 在化学感觉神经元中表达的气味受体的大家族。当前 一种假说认为气味受体在嗅觉中有两种不同的作用， 功能：调节气味反应并影响轴突的布线 投射到嗅球。这个想法提出了一些重要的问题， 什么信息被映射到大脑表面。这些目标 研究的目的是开始阐明这两个角色之间的关系。的 第一个目的是确定OR的不同功能（配体结合）是否 和轴突引导）可以分离。这将通过创建小鼠品系来完成 在确定的内源性气味受体基因座中具有靶向基因突变， 分析荧光标记的神经元表达的气味特异性， 定义的受体，并将这些数据与观察到的轴突寻路 体内行为第二个目的是确定气味特异性或 受体序列与神经元投射的位置相关， 由一组特定基因表达的气味受体控制。气味剂 将测量反应谱，并对表达的受体进行测序， 投射到嗅球局部区域的传入神经由 基因标记神经元的投射。解决这些问题提供了 了解哺乳动物神经系统如何代表 化学信息基因打靶和光学成像的结合， 神经元活动为研究信息编码提供了强有力的工具 在哺乳动物的嗅觉系统中。靶向表达的一般方法 外源蛋白（例如，遗传编码的光学指示器）来定义 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.