Taste-independent regulation of nutrient intake in Drosophila.

为了维持营养动态平衡，动物必须有强大的系统来控制营养摄入量。例如，味觉在识别营养物质以供消费方面起着重要作用。然而，越来越多的证据表明，动物也使用不依赖味道的机制来检测摄取后的特定营养物质，并指导它们的摄食行为。我们和其他人最近证明，苍蝇使用摄食后传感器来根据特定糖的营养价值调整它们的摄食决定。我提出的探索基金研究计划的长期目标是利用果蝇黑腹果蝇强大的分子、遗传和行为工具，解开调节几种关键营养物质-盐、氨基酸、水和脂肪-的摄取的不依赖味道的神经机制。 我们对未来五年有三个具体目标： 目的1：表征各种营养素对消费和奖励的非味觉影响，以及这些影响依赖于先前的营养剥夺。利用缺乏味觉输入的突变体，我们将分离出偏爱盐、氨基酸、水和脂肪的非味觉成分。我们还将使用经典的条件记忆分析来评估每种营养物质对大脑奖励系统的影响。 目的2：揭示摄食后营养感知机制的神经肽能调节剂。众所周知，神经肽在连接内部状态和行为方面发挥着重要作用。我们将使用神经元沉默和RNA干扰筛选来识别和表征调节每种关键营养物质消耗的神经肽。 目的3：解剖非味觉营养感觉与行为之间的神经通路。我们将使用遗传编码的神经元消音器和激活器来探索特定神经元在营养寻找行为中的功能。我们还将使用功能成像和电生理学来描述营养摄入后这些神经元活动的变化。 这项拟议的研究利用了功能强大的苍蝇遗传工具包来了解检测摄取营养物质的复杂过程，然后改变行为以促进适当的摄入量。这是一个基本的生物学问题，它将为神经电路如何处理感觉信息，信息处理如何受到内部代谢状态的影响，以及如何在短期和长期时间尺度上控制行为提供洞察。 除了提高对大脑功能的认识外，我们对昆虫取食调节机制的研究将在害虫防治方面具有重要应用，这将对加拿大和世界各地的经济和环境产生深远影响。

In order to maintain nutrient homeostasis, animals must have robust systems to control nutrient intake. For example, the sense of taste plays an important role in identifying nutrients for consumption. However, mounting evidence suggests that animals also use taste-independent mechanisms to detect specific nutrients following ingestion and guide their feeding behavior. We and others have recently demonstrated that flies use post-ingestive sensors to adjust their feeding decisions according to the nutritive value of specific sugars. The long-term goal of my proposed Discovery Grant research program is to use the powerful molecular, genetic, and behavioral tools of the fruit fly, Drosophila melanogaster, to unravel the taste-independent neuronal mechanisms regulating intake of several key nutrients - salt, amino acids, water, and fats. We have three specific aims for the next five years: Aim 1: To characterize the taste-independent impact of various nutrients on consumption and reward, and the dependence of these effects on prior nutrient deprivation. Using mutants lacking taste input, we will isolate the taste-independent component of preference for salt, amino acids, water, and fats. We will also use classical conditioning memory assays to assess the impact of each nutrient on brain reward systems. Aim 2: To uncover neuropeptidergic modulators of post-ingestive nutrient sensing mechanisms. Neuropeptides are known to play important roles in linking internal states and behavior. We will use neuronal silencing and RNA-interference screens to identify and characterize neuropeptides regulating the consumption of each key nutrient. Aim 3: To dissect the neural pathways linking taste-independent nutrient sensing with behavior. We will use genetically encoded neuronal silencers and activators to probe the function of specific neurons in nutrient seeking behavior. We will also use functional imaging and electrophysiology to characterize changes in the activity of those neurons following nutrient ingestion. The proposed research leverages the powerful fly genetic toolkit to understand the complex process of detecting ingested nutrients and then altering behavior to promote appropriate levels of intake. This is a fundamental biological problem that will provide insight into how neural circuits process sensory information, how information processing is affected by internal metabolic states, and how behavior is controlled on short- and long-term time scales. In addition to advancing knowledge of brain function, our research on the mechanisms regulating insect feeding will have important applications in pest control, which profoundly impacts the economy and environment in Canada and around the world.