Genetic Analysis of Olfactory Coding in Drosophilia

嗅觉系统允许动物感知大量的关键环境刺激， 食物、捕食者或配偶的存在。不同物种嗅觉分子生物学研究进展 我发现了这些统一的原则：一个给定的嗅觉神经元表达一种或几种特定的气味 受体基因;所有表达一种气味受体的神经元都集中在有限数量的目标上，称为 在大脑中的肾小球;气味刺激引起大脑中肾小球激活的定型模式。但如何 对气味的有意识感知是在大脑中编码的还不清楚。 这项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， 解剖学上简单的嗅觉系统适合于行为遗传分析。 初步研究表明，幼虫尖端背器中的21个神经元介导了所有的神经元活动。 对挥发性刺激的嗅觉反应;一个以前没有特征的至少18种果蝇气味的子集 受体基因编码幼虫的气味受体;一个给定的嗅觉神经元表达一个或几个 这些气味受体基因和目标是一个专门的肾小球在幼虫的大脑;基因消融一个 单个嗅觉神经元导致嗅觉行为的选择性改变。这些结果确立了果蝇 幼虫是已知的最简单的基因操纵模式生物，包含所有关键的细胞元素 在脊椎动物嗅觉系统中发现，并为在基因，神经元， 电路和行为。 这些研究已经导致了这样的假设，即表达不同功能的嗅觉神经元的组合激活， 需要气味受体来编码给定气味的显著特征并激活适当的 行为输出为了验证这一假设，提出了以下具体目标：（1）分离完整的 幼虫气味受体基因库。(2)决定幼虫的外围和中央组织 嗅觉神经元(3)阐明已鉴定的幼虫嗅觉神经元的行为输出。健康 这些研究的相关性在于，对感官知觉背后的回路的理解与大脑 具有神经或精神基础的疾病。

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.