Taste Representations in the Drosophila Brain

描述（由申请人提供）：本提案的长期目标是增加对味觉识别和味觉感知的理解。果蝇的味觉系统为味觉识别的研究提供了一个极好的模型，因为它与定义明确的化学线索、强大的行为反应和一个复杂的神经系统相关联，可以适应分子、遗传和电生理方法。果蝇的味觉识别是由长鼻、内部口器、腿、翅膀和产卵器上的味觉神经元介导的。最近的研究已经确定了苍蝇的三种味觉细胞群：糖、苦和二氧化碳感知细胞。拟议的研究扩展了这项工作，目的是确定检测特定口味的分子机制。在哺乳动物中，G蛋白偶联受体介导糖、氨基酸和苦味化合物的检测，而离子通道则检测盐和酸。在果蝇中，一个大的候选味觉受体基因家族在糖和苦味感知细胞中表达，并可能介导这些味觉的检测。然而，检测其他口味的分子机制尚未确定。在初步研究中，微阵列分析，结合原位杂交和转基因实验，确定了新的味道特异性分子。提出的实验旨在确定这些味觉特异性分子的功能，目的是增加对周边味觉识别的理解。公共卫生相关性：本研究的重点是昆虫味觉检测的分子机制。阐明果蝇味觉神经元检测化学物质的分子机制将为研究昆虫的化学物质检测提供基础。人类疾病的昆虫载体利用化学识别来瞄准它们的人类宿主，并对疟疾、伤寒、霍乱和沙眼等毁灭性疾病的传播负责。确定模式生物中果蝇化学检测的分子机制对于鉴定携带疾病的昆虫的同源物是必不可少的，这是鉴定受体拮抗剂以操纵宿主识别的必要的第一步。此外，识别果蝇的味觉受体将提示可能参与人类味觉检测的候选分子。

DESCRIPTION (provided by applicant): The long-term goal of this proposal is to increase understanding of taste recognition and taste perception. The gustatory system of Drosophila provides an excellent model for studies of taste recognition because it is associated with well-defined chemical cues, robust behavioral responses and a complex nervous system that is amenable to molecular, genetic and electrophysiological approaches. Taste recognition in Drosophila is mediated by gustatory neurons on the proboscis, internal mouthparts, legs, wings and ovipositor. Recent studies have identified three taste cell populations in the fly: sugar-, bitter-, and carbon dioxide-sensing cells. The proposed studies expand on this work, with the aim of identifying molecular mechanisms underlying the detection of specific tastes. In mammals, G protein-coupled receptors mediate detection of sugars, amino acids, and bitter compounds, whereas ion channels detect salts and acids. In Drosophila, a large family of candidate gustatory receptor genes is expressed in sugar and bitter-sensing cells and is likely to mediate detection of these tastes. However, the molecular mechanisms underlying the detection of other tastes are not established. In preliminary studies, microarray analyses, combined with in situ hybridization and transgenic experiments, identified novel taste-specific molecules. The proposed experiments are designed to determine the function of these taste-specific molecules with the aim of increasing understanding of taste recognition in the periphery. PUBLIC HEALTH RELEVANCE: This research focuses on the molecular mechanisms of taste detection in insects. Elucidating the molecular mechanisms underlying detection of chemical compounds by Drosophila gustatory neurons will provide basic insight into chemical detection by insects. Insect carriers of human disease use chemical recognition to target their human hosts and are responsible for the spread of devastating diseases such as malaria, typhoid, cholera and trachoma. Defining the molecular mechanisms of chemical detection in the model organism Drosophila is essential in order to identify homologues in disease-carrying insects, a necessary first step toward identifying receptor antagonists to manipulate host recognition. In addition, identifying taste receptors in Drosophila will suggest candidate molecules that may participate in taste detection in humans.