Taste Receptor Genes and Sensory Coding

描述(申请人提供)：化学感官知觉为所有生物体，从细菌到人类，提供有关外部世界化学成分的基本信息。在昆虫和脊椎动物中，这个“化学世界”通常由两种不同的感官方式感知，即味觉和嗅觉。我们的长期目标是了解动物如何识别环境中存在的化学线索，并调查这些线索是如何调节摄食行为的。行为和电生理研究表明，果蝇具有发达的味觉，能够探测到大量不同的化学底物(配体)。遗传学在生物学几乎所有学科中的广泛影响使果蝇成为分子和行为神经生物学中非常有价值的模型系统。它的作用在揭示化学感觉的逻辑方面具有特别重要的意义，因为它的化学感觉系统与脊椎动物/哺乳动物的化学感觉系统有许多相似之处，还因为它也是昆虫的模型系统，其中许多昆虫对人类的繁荣和健康有直接影响。果蝇味觉受体神经元(GRN)表达7种跨膜受体(味觉受体或GRs)，可检测可溶性配体。GRN的激活被传播到CNS的味觉中心，将感觉输入转化为各种行为输出。这些行为品味反应大致可分为接受行为或回避行为。最近几个实验室的工作表明，接受和回避行为是由两个分子上不同的GRN亚群(“甜”和“苦”神经元)介导的，每一个亚群都表达不同的GR组。有趣的是，个别神经元亚群表达部分重叠但不完全相同的可能感觉苦味的GRs成员，这表明苍蝇可以区分不同的“苦味”味道。分子遗传学方法，结合行为学和电生理学的研究，也导致了糖味受体的识别，这种受体也在复杂和重叠的“甜味”神经元中表达。最后，这些研究还证实了味觉受体是由不同GR组成的多聚体复合体。然而，尽管取得了所有这些进展，关于味觉感受器本身的许多基本问题，以及味觉器官中化学物质的检测如何转化为对大脑味觉质量的感知，仍然没有答案。这个应用程序将调查其中一些问题。我们建议确定GRs的膜拓扑结构和信号模式。此外，我们将使用分子遗传和行为分析来研究糖受体的异构体组成，最后，我们将测试苍蝇是否有能力区分苦味通道中的不同味道。

DESCRIPTION (provided by applicant): Chemosensory perception provides all organisms, from bacteria to humans, with essential information about the chemical composition of the external world. In insects and vertebrates, this 'chemical world' is generally perceived by two distinct sensory modalities, gustation and olfaction. Our long-tem objective is to understand how animals recognize chemical cues present in their environment and to investigate how these cues regulate feeding behaviors. Behavioral and electrophysiological studies have indicted that Drosophila possesses a well-developed sense of taste that can detect a large number of chemically diverse substrates (ligands). The broad impact of genetics in virtually all disciplines of biology has made Drosophila an extremely valuable model system in molecular and behavioral neurobiology. Its role has been of particular significance in uncovering the logic of chemosensory perception, because its chemosensory systems exhibit many parallels with those of vertebrates/mammals, and because it also serves as a model system for insects, many of which have a direct impact on human prosperity and health. Drosophila gustatory receptor neurons (GRNs) express putative seven transmembrane receptors (Gustatory Receptors or GRs) that detect soluble ligands. Activation of GRNs is propagated to taste centers in the CNS, which translate sensory input into various behavioral outputs. These behavioral taste responses can be broadly divided into acceptance behavior or avoidance behavior. Recent work in several laboratories has shown that acceptance and avoidance behaviors are mediated by two molecularly distinct subpopulations of GRNs ("sweet" and "bitter" neurons), each expressing different sets of GRs. Interestingly, individual neuron subpopulations express partially overlapping but not identical members of putative bitter-sensing GRs, suggesting that flies can discriminate distinct qualities of "bitter" taste. Molecular-genetics approaches, combined with behavioral and electrophysiological studies have also led to the identification of sugar taste receptors, which are also expressed in complex and overlapping sets of "sweet" neurons. Finally, these studies also established evidence that taste receptors are multimeric complexes composed of different GRs. Yet, despite all this progress, many basic questions about the taste receptors themselves, and about how detection of chemicals in taste organs is translated in the percept of a taste quality in the brain, remain unanswered. This application will investigate some of these questions. We propose to determine membrane topology and mode of signaling of GRs. Furthermore, we will investigate the heteromeric composition of sugar receptors using molecular genetic and behavioral analyses, and lastly, we shall test whether flies have the ability to discriminate between different flavors within the bitter taste modality.