Receptors and Neurons Mediating Acid Taste in Drosophila

描述(由申请人提供)：各种化学刺激被检测到的机制以及如何转化为适当的行为是味觉神经生物学的中心问题。这项建议的主要目的是研究果蝇羧酸味道的分子和细胞机制，并确定蚊子对羧酸的神经生理反应。果蝇是研究昆虫味觉系统的基本逻辑的一个很好的模型。虽然在破译包括甜味和苦味化合物在内的某些类别味觉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。在前期研究的基础上，这一建议的中心假设是，酸刺激可以激活和抑制不同类别的味觉神经元，而酸介导的味觉神经元抑制依赖于高度保守的离子性受体家族成员Ir25a的功能。验证这一假说的方法将是：1)进行电生理分析，以表征羧酸对味觉神经元的激活；2)验证酸刺激激活的味觉神经元的特性，并确定它们在酸厌恶行为中的作用；3)表征酸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)启动埃及伊蚊味觉神经元对酸的兴奋和抑制反应的分析。这项拟议的研究具有创新性，因为它与之前专注于嗅觉系统作用的羧酸化学感觉反应研究有所不同，因为研究计划涵盖了跨越遗传、电生理和行为分析的多学科方法。这项拟议的研究具有重要意义，因为它将提供对酸味在一个有价值的模式生物中的分子和细胞基础的洞察，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埃及伊蚊和冈比亚按蚊等人类吸血昆虫的行为很重要，这些昆虫传播致命的疾病。了解进化上保守的受体在检测羧酸中的作用可能会导致控制节肢动物病媒的新策略。 公共卫生相关性：我们将调查果蝇和埃及伊蚊对羧酸的味觉反应，这是一类由昆虫味觉神经元检测的化学物质，人们对其知之甚少。我们建议通过味觉神经元研究苍蝇和蚊子共有的受体在酸性检测中的功能。低挥发性的羧酸对于黄热病蚊子埃及伊蚊等疾病媒介在选择宿主和产卵地点时可能是重要的。了解进化上保守的受体在酸性反应中的作用，可能会为昆虫控制提供新的靶点。

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.