Taste-independent regulation of nutrient intake in Drosophila.

为了维持营养平衡，动物必须有强大的系统来控制营养摄入。例如，味觉在识别食用营养素方面起着重要作用。然而，越来越多的证据表明，动物也使用味觉独立的机制来检测摄入后的特定营养素，并指导其进食行为。我们和其他人最近已经证明，苍蝇使用摄食后的传感器，以调整他们的喂养决定根据特定的糖的营养价值。我提出的发现资助研究计划的长期目标是利用果蝇强大的分子、遗传和行为工具，解开调节几种关键营养素盐、氨基酸、水和脂肪摄入的非味觉神经机制。我们在未来五年有三个具体目标：目标1：描述各种营养素对消耗和奖励的非味觉影响，以及这些影响对先前营养素剥夺的依赖性。使用缺乏味觉输入的突变体，我们将分离出对盐、氨基酸、水和脂肪的偏好的味觉独立成分。我们还将使用经典的条件反射记忆测定来评估每种营养素对大脑奖励系统的影响。目的2：揭示神经肽能调节剂的摄食后营养感应机制。已知神经肽在连接内部状态和行为中起重要作用。我们将使用神经元沉默和RNA干扰筛选，以确定和表征神经肽调节消费的每一个关键nutrients.Aim 3：解剖的神经通路连接味觉无关的营养感知与行为。我们将使用基因编码的神经元沉默剂和激活剂来探测特定神经元在营养寻求行为中的功能。我们还将使用功能成像和电生理学来表征营养摄入后这些神经元活动的变化。拟议的研究利用强大的苍蝇遗传工具包来了解检测摄入的营养素的复杂过程，然后改变行为以促进适当的摄入水平。这是一个基本的生物学问题，将提供洞察神经回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。除了推进对大脑功能的认识，我们对昆虫摄食调节机制的研究将在害虫防治中具有重要的应用，这将深刻影响加拿大和世界各地的经济和环境。

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.