Receptors and Neurons Mediating Acid Taste in Drosophila

介导果蝇酸味的受体和神经元

• 批准号: 8385434
• 负责人: Anupama Arun Dahanukar
• 金额: $ 18.25万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8385434
• 关键词: Acids; Aedes; Animal Model; Anopheles gambiae; Arthropods; Behavior; Behavioral; Blood; Carboxylic Acids; Categories; Cells; Chemicals; Code; Culicidae; Detection; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Family; Foundations; Genetic; Goals; Human; Insect Control; Insecta; Investigation; Lead; Link; Logic; Mammals; Maps; Measures; Mediating; Modality; Modeling; Molecular; Neurobiology; Neurons; Pattern; Physiological; Proteins; Research; Role; Series; Site; Specific qualifier value; Stimulus; Sucrose; Sweat; Sweating; System; Taste Perception; Testing; Transgenic Organisms; Translating; Water; Yellow Fever; base; egg; feeding; fly; innovation; insight; interdisciplinary approach; member; mutant; neurophysiology; novel; novel strategies; receptor; receptor function; research study; response; sensor; success; sugar; vector mosquito

DESCRIPTION (provided by applicant): The mechanisms by which various classes of chemical stimuli are detected and how that translates into appropriate behaviors is a central problem in gustatory neurobiology. The overarching objective of this proposal is to investigate the molecular and cellular mechanisms of carboxylic acid taste in Drosophila, and to identify neurophysiological responses to carboxylic acids in the mosquito, Aedes aegypti. Drosophila is an excellent model to study the fundamental logic by which the taste system is organized in insects. While a lot of progress has been made in deciphering the molecular and cellular mechanisms of certain categories of tastants including sweet and bitter compounds, little is known about the fly's taste responses to acids. Based on preliminary studies, the central hypothesis of this proposal is that acid stimuli can activate and inhibit different categories of taste neurons, and acid-mediated inhibition of taste neurons is dependent on the function of a highly conserved member of the Ionotropic receptor family, Ir25a. The approach to test this hypothesis will be to: 1) undertake electrophysiological analyses to characterize activation of taste neurons by carboxylic acids, 2) validate the identity of taste neurons that are activated in response to acid stimuli and determine their contribution in acid aversion behavior, 3) characterize acid-mediated inhibition of sweet neurons, 4) link the function of Ir25a to acid-mediated inhibition of sugar neurons, and 5) initiate an analysis of excitatory and inhibitory responses to acids in taste neurons of Aedes aegypti. The proposed research is innovative because it represents a departure from previous studies of chemosensory responses to carboxylic acids that focused on the role of the olfactory system, and because the research plan encompasses a multidisciplinary approach spanning genetic, electrophysiological and behavioral analyses. The proposed research is significant because it will provide insight into the molecular and cellular basis of acid taste in a valuable model organism, which will aid in studying fundamental problems of chemosensory coding and behavior. Notably, carboxylic acids of low volatility are components of human sweat and their detection by taste neurons may be important for behaviors of human blood-feeding insects such as Aedes aegypti and Anopheles gambiae, which transmit deadly diseases. An understanding of the function of evolutionarily conserved receptors in the detection of carboxylic acids may lead to novel strategies for control of arthropod disease vectors. PUBLIC HEALTH RELEVANCE: We will investigate taste responses of Drosophila and Aedes aegypti to carboxylic acids, a class of chemicals whose detection by insect taste neurons is poorly understood. We propose to study the function of a receptor that is shared between flies and mosquitoes in acid detection by taste neurons. Carboxylic acids of low volatility are may be important for disease vectors such as the yellow fever mosquito Aedes aegypti in selecting hosts and egg-laying sites. An understanding of evolutionarily conserved receptors that function in acid response may offer novel targets for insect control.

描述（由申请人提供）：检测各种化学刺激的机制以及如何将其转化为适当的行为是味觉神经生物学的核心问题。本研究的主要目的是研究果蝇对羧酸味觉的分子和细胞机制，并确定埃及伊蚊对羧酸的神经生理反应。果蝇是研究昆虫味觉系统组织的基本逻辑的绝佳模型。虽然在破译某些种类的味觉物质（包括甜味和苦味化合物）的分子和细胞机制方面取得了很大进展，但对果蝇对酸的味觉反应知之甚少。基于初步的研究，该提议的中心假设是酸刺激可以激活和抑制不同类别的味觉神经元，酸介导的味觉神经元的抑制依赖于嗜离子受体家族中高度保守的成员Ir25a的功能。检验这一假设的方法是：1)进行电生理分析，以表征羧酸对味觉神经元的激活；2)验证在酸刺激下激活的味觉神经元的身份，并确定它们在酸厌恶行为中的作用；3)表征酸介导的甜味神经元抑制；4)将Ir25a的功能与酸介导的糖神经元抑制联系起来。5)开始分析埃及伊蚊味觉神经元对酸的兴奋性和抑制性反应。这项提议的研究具有创新性，因为它代表了对羧酸化学感觉反应的先前研究的背离，这些研究主要集中在嗅觉系统的作用上，而且因为这项研究计划涵盖了多学科的方法，包括遗传、电生理和行为分析。这项研究具有重要意义，因为它将为有价值的模式生物提供酸味的分子和细胞基础，这将有助于研究化学感觉编码和行为的基本问题。值得注意的是，低挥发性的羧酸是人类汗液的组成部分，味觉神经元对它们的检测可能对人类吸血昆虫（如埃及伊蚊和冈比亚按蚊）的行为很重要，这些昆虫会传播致命疾病。了解进化保守受体在检测羧酸中的功能可能会导致节肢动物疾病媒介控制的新策略。