Receptors and Neurons Mediating Acid Taste in Drosophila

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中心问题。该提案的总体目标是研究果蝇中羧酸味觉的分子和细胞机制，并确定蚊子，埃及伊蚊中羧酸的神经生理反应。果蝇是研究昆虫味觉系统基本逻辑的极好模型。虽然在破译某些类别的促味剂（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，但对苍蝇对酸的味觉反应知之甚少。基于初步研究，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，并且酸介导的味觉神经元抑制依赖于离子型受体家族的高度保守成员Ir25a的功能。检验这一假设的方法是：1）进行电生理学分析以表征羧酸对味觉神经元的激活，2）验证响应于酸刺激而激活的味觉神经元的身份并确定它们在酸厌恶行为中的贡献，3）表征酸介导的对甜味神经元的抑制，4）将Ir25a的功能与酸介导的糖神经元抑制联系起来，以及5）开始分析埃及伊蚊味觉神经元中对酸的兴奋性和抑制性反应。拟议的研究是创新的，因为它代表了对羧酸的化学感觉反应的先前研究的偏离，这些研究侧重于嗅觉系统的作用，并且因为研究计划包括跨遗传，电生理和行为分析的多学科方法。这项研究意义重大，因为它将深入了解有价值的模式生物中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成分，它们被味觉神经元检测到可能对人类吸血昆虫的行为很重要，如埃及伊蚊和冈比亚按蚊，它们传播致命的疾病。了解进化上保守的受体在检测羧酸的功能，可能会导致新的策略控制节肢动物疾病的媒介。

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.