Genetic Analysis of Olfactory Coding in Drosophilia

果蝇嗅觉编码的遗传分析

• 批准号: 6868294
• 负责人: Leslie B Vosshall
• 金额: $ 33.4万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-02 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868294
• 关键词: Drosophilidae; behavior test; behavioral genetics; chemoreceptors; cytogenetics; green fluorescent proteins; in situ hybridization; larva; molecular genetics; neuroanatomy; neurons; nucleic acid sequence; olfactions; olfactory stimulus; polymerase chain reaction; receptor expression; sensory discrimination

DESCRIPTION (provided by applicant): The olfactory system permits animals to perceive a vast number of critical environmental stimuli signaling the presence of food, predators, or mates. Recent advances in the molecular biology of olfaction in diverse species have uncovered these unifying principles: a given olfactory neuron expresses one or a few specific odorant receptor genes; all neurons expressing one odorant receptor converge upon a limited number of targets called glomeruli in the brain; odor stimuli elicit stereotyped patterns of glomerular activation in the brain. However, how the conscious perception of an odor is encoded in the brain is unclear. The long-term goals of this proposal are to understand the molecular and cellular basis for odor coding. Experiments will be carried out in the larval stage of the fruit fly, Drosophila melanogaster, which has an anatomically simple olfactory system amenable to behavior genetic analysis. Preliminary studies have demonstrated that 21 neurons in the dorsal organ at the tip of the larva mediate all olfactory responses to volatile stimuli; that a previously uncharacterized subset of at least 18 Drosophila odorant receptor genes encodes the larval odorant receptors; that a given olfactory neuron expresses one or a few of these odorant receptor genes and targets a dedicated glomerulus in the larval brain; that genetic ablation of a single olfactory neuron leads to selective alterations in olfactory behavior. These results establish the Drosophila larva as the simplest known genetically manipulable model organism that contains all the critical cellular elements found in vertebrate olfactory systems, and set the stage for analyzing odor coding at the level of genes, neurons, circuits, and behavior. These studies have led to the hypothesis that combinatorial activation of olfactory neurons expressing different odorant receptors is required to encode the salient features of a given odorant and activate the appropriate behavioral output. To test this hypothesis, the following specific aims are proposed: (1) Isolating the complete repertoire of larval odorant receptor genes. (2) Determining the peripheral and central organization of larval olfactory neurons. (3) Elucidating the behavioral output of identified larval olfactory neurons. The health relatedness of these studies is that an understanding of circuits underlying sensory perception is relevant for brain disorders with a neurological or psychiatric basis.

描述（由申请人提供）：嗅觉系统使动物能够感知大量关键的环境刺激，这些刺激表明食物、捕食者或配偶的存在。不同物种嗅觉分子生物学的最新进展揭示了这些统一原理：特定的嗅觉神经元表达一个或几个特定的​​气味受体基因；所有表达一种气味受体的神经元都会聚集在大脑中称为肾小球的有限数量的目标上；气味刺激会引起大脑中肾小球激活的刻板模式。然而，大脑对气味的有意识感知是如何编码的尚不清楚。 该提案的长期目标是了解气味编码的分子和细胞基础。实验将在果蝇（Drosophila melanogaster）的幼虫阶段进行，该果蝇具有解剖学上简单的嗅觉系统，适合行为遗传分析。 初步研究表明，幼虫尖端的背器官中的21个神经元介导对挥发性刺激的所有嗅觉反应；至少 18 个果蝇气味受体基因的先前未表征的子集编码幼虫气味受体；特定的嗅觉神经元表达一种或几种气味受体基因，并针对幼虫大脑中的专用肾小球；单个嗅觉神经元的基因消融会导致嗅觉行为的选择性改变。这些结果将果蝇幼虫确立为已知的最简单的基因可操纵模型生物，它包含脊椎动物嗅觉系统中发现的所有关键细胞元件，并为在基因、神经元、回路和行为水平上分析气味编码奠定了基础。 这些研究提出了这样的假设：表达不同气味受体的嗅觉神经元需要组合激活来编码给定气味的显着特征并激活适当的行为输出。为了检验这一假设，提出了以下具体目标：（1）分离幼虫气味受体基因的完整库。 (2)确定幼虫嗅觉神经元的外周和中枢组织。 (3) 阐明已识别的幼虫嗅觉神经元的行为输出。这些研究与健康的相关性在于，对感觉知觉背后的回路的理解与具有神经学或精神病学基础的脑部疾病相关。