Molecular Analysis of Olfactory Sensory Imputs

描述（来自申请人的摘要）：嗅觉系统类似于 其他感觉系统将感觉刺激转化为不同的 感知。然而，它提供了独特的机会， 阐明如何从感官刺激中提取信息的方法， 然后在大脑中组织起来产生不同的感知。这个机会 源于发现气味检测是由大约1000种 不同的气味受体（ORs），其由嗅觉传感器表达 神经元（OSNs）在鼻嗅上皮（OE）。从OE，信号是 通过嗅觉公牛（OB），然后嗅觉皮层（OC）， 其他脑区。每个OSN表达一个OR基因。在OE中，4个区域表示 不同的手术室表达相同OR的OSN分散在一个区域中。 然而，它们的轴突聚集在一些特定的OB肾小球中，产生一个神经元。 手术室输入的精确映射。的模式化的功能意义 OE和OB尚未被理解，也不知道OR输入是如何组织的 除了OB。另一个重要的问题是， 气味结构被组织以产生不同的气味感觉。最近 我们发现不同的气味可以通过不同的 手术室一个单一的气味被高度相关和不同的OR识别， 和一些ORs之间的区别气味，不同的是一个单一的功能 而其他人则没有。 在本建议书所述的研究中，我们将进一步探讨如何 嗅觉信息通过OR家族从气味结构获得。我们 也将研究这些信息是如何在嗅觉系统中组织起来的。我们 将首先使用OSN的钙成像和单细胞PCR的组合， 确定具有相同碳链的n-脂肪族增味剂的OR，但 不同的功能群。然后我们将每个OR表示为 细胞系，并进一步表征其气味特异性。基于我们 以前的研究结果，我们希望确定高度相关和不同的OR， 其中一些将区分官能团不同气味剂， 其他人不会。使用原位杂交，我们将询问是否 OR的功能或其结构之间存在相关性， OE中的区域或OB中肾小球的特殊排列。 最后，我们将使用基因靶向来产生共表达a 跨神经元示踪剂与单个OR基因，以确定如何输入 在OC中组织来自各个OR的输入， 具有不同官能团的气味剂靶向于特定的皮质 地区

DESCRIPTION (From the Applicant's Abstract): The olfactory system resembles other sensory systems in its ability to translate sensory stimuli into distinct perceptions. However, it offers unique opportunities to use molecular approaches to elucidate how information is extracted from sensory stimuli and then organized in the brain to yield different perceptions. This opportunity stems from the finding that odorant detection is mediated by approximately 1000 different odorant receptors (ORs), which are expressed by olfactory sensor neurons (OSNs) in the nasal olfactory epithelium (OE). From the OE, signals are relayed through the olfactory bull (OB) and then the olfactory cortex (OC) to other brain areas. Each OSN expresses one OR gene. In the OE, 4 zones express different sets of ORs. OSNs expressing the same OR are scattered in one zone. However, their axons converge in a few specific OB glomeruli, generating a precise map of OR inputs. The functional significance of the patterning of the OE and OB is not yet understood, nor is it known how OR inputs are organized beyond the OB. Another important question is how information about diverse odorant structures is organized to yield different odor perceptions. Recently we found that different odorants are recognized by different combinations of ORs. A single odorant was recognized by both highly related and divergent ORs, and some ORs distinguished among odorants that differed by a single functional group whereas others did not. In the studies described in this proposal, we will further explore how olfactory information is obtained from odorant structures by the OR family. We will also examine how that information is organized in the olfactory system. We will first use a combination of calcium imaging of OSNs and single cell PCR to identify ORs for n-aliphatic odorants that have the same carbon chains, but a variety of different functional groups. We will then express each of the ORs in a cell line and further characterize their odorant specificities. Based on our previous findings, we expect to identify both highly related and divergent ORs, some of which will distinguish odorants that differ in functional group and others that will not. Using in situ hybridization, we will then ask whether there are correlations between the function of an OR, or its structure, and either zones in the OE or the particular arrangement of glomeruli in the OB. Finally, we will use gene targeting to generate mice that coexpress a transneuronal tracer with a single OR gene in order to determine how inputs from individual ORs are organized in the OC and whether inputs from ORs for odorants with different functional groups are targeted to specific cortical regions.