A Neuropeptidergic Neural Network Integrates Taste with Internal State to Modulate Feeding

喂食是一种基本的行为，受到严格的监管，以精确地满足动物的新陈代谢需求。 关于食物，动物必须做出的首要决定是摄取还是拒绝。物质 具有高营养价值的食物被摄取，而毒素和有害物质被拒绝。为了做出这个决定， 这种动物依靠它的味觉来评价食物的质量。大多数动物对甜蜜和 有不同刻板印象的苦味者：甜味物质，通常富含卡路里，具有食欲和 被接受，而通常有害的苦味化合物被拒绝和避免。另一个重要的部分是 决定是否摄取或拒绝潜在的食物是动物的新陈代谢需要，这是由 在饥饿和饱足之间取得平衡。动物内部状态的这一方面是通过 各种激素和神经调节剂之间错综复杂的平衡，一些是饥饿的信号，另一些是信号 饱腹感。不同荷尔蒙和神经调节剂的协同作用如何影响进食是一个领域 由于摄食行为失调会导致肥胖或营养不良及其相关因素，人们对此非常感兴趣 病态。 在这个提议中，我们集中在果蝇的一个神经调节性神经元网络上，在这个网络中，一个神经调节剂 被称为Leucokinin的是由网络中的某些神经元亚群分泌的，并被其他神经元检测到。我们 建议检验神经调节神经元的亮氨酸激肽网络整合信息的假设 关于味道质量和苍蝇的内部状态来调节取食行为。在这个网络中，一组 神经元接受来自另外两个神经元的输入：来自其中一个的味觉信息和关于内部状态的信息 动物与其他动物的区别。受体神经元整合这两个信息流，并反过来调制 通过分泌其他调节摄食的神经肽来控制摄食行为。为了检验这一假设，我们使用一个 多管齐下的方法，包括解剖、功能和行为分析。在我们提议的研究中，我们 使用最先进的技术标记神经元连接并操纵选择性亚群的活动 以检查这些手法的行为和功能影响。我们还开发了一种新的 研究神经调节部位的技术。这项技术能够有选择地、不偏不倚地、全脑地 具有细胞分辨率的特定调节剂对神经调节部位的检查。因此，我们的研究将 加深我们对摄食调节的理解，并为研究神经调节提供新的工具 随着更多模式生物的神经连接图变得越来越重要，研究领域将变得更加重要 可用。

Feeding is a fundamental behavior that is tightly regulated to precisely meet the metabolic needs of the animal. The primary decision that an animal must make regarding food is whether to ingest it or reject it. Substances with high nutritional value are ingested, while toxins and harmful substances are rejected. To make this decision, the animal relies on its sense of taste to evaluate the quality of the food. Most animals respond to sweet and bitter tastants with different stereotyped behaviors: sweet substances, often calorie rich, are appetitive and accepted, while bitter compounds, usually harmful, are rejected and avoided. Another important part of the decision whether to ingest or reject potential food is the metabolic need of the animal that is manifested by the balance between hunger and satiety. This aspect of the internal state of the animals is evaluated through an intricate balance between various hormones and neuromodulators, some signal hunger while the others signal satiety. How the concerted action of the various hormones and neuromodulators affects feeding is an area of significant interest as dysregulation of feeding behavior results in obesity or in malnutrition and their associated morbidities. In this proposal, we focus on one network of neuromodulatory neurons in Drosophila in which a neuromodulator termed leucokinin is secreted by certain subsets of neurons within the network and detected by others. We propose to test the hypothesis that the leucokinin network of neuromodulatory neurons integrates information about taste quality and the internal state of the fly to modulates feeding behavior. In this network, one set of neurons receives inputs from two others: taste information from one, and information about the internal state of the animal from the other. The recipient neurons integrate the two streams of information and in turn modulate feeding behavior by secreting other neuropeptides that regulate feeding. To test this hypothesis, we use a multipronged approach that includes anatomical, functional and behavioral analyses. In our proposed study, we use state of the art techniques to label neuronal connectivity and to manipulate the activity of selective subsets of neurons to examine the behavioral and functional effects of these manipulations. We also develop a new technique for studying sites of neuromodulation. This technique enables selective, unbiased, brain-wide examination of sites of neuromodulation by specific modulators with cellular resolution. Thus, our studies will deepen our understanding of the regulation of feeding and provide new tools to study neuromodulation, a research area that will increase in importance as neural connectivity maps of more model organisms become available.