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

神经肽能神经网络将味觉与内部状态相结合来调节进食

• 批准号: 10734258
• 负责人: Gilad Barnea
• 金额: $ 45.29万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-08 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734258
• 关键词: Abdomen; Address; Adult; Affect; Agriculture; Anatomy; Animals; Anterior; Area; Behavior; Behavioral; Brain; Calcium; Calories; Complement; Data; Decision Making; Desire for food; Digestion; Discrimination; Disease; Disease Vectors; Diuretics; Drosophila genus; Equilibrium; Evaluation; Exposure to; Feeding behaviors; Food; Food Preferences; Glucagon; Glucose; Health; Hemolymph; Hormones; Horns; Human; Hunger; Image; Ingestion; Insect Control; Insecta; Ion Transport; Label; Lateral; Location; Malnutrition; Malpighian Tubules; Mammals; Maps; Metabolic; Methods; Morbidity - disease rate; Mushroom Bodies; Nerve; Neuromodulator; Neurons; Neuropeptides; Neuropil; Nutrient; Nutrition Assessment; Nutritional; Obesity; Organ; Peptide Transport; Process; Publishing; Receptor Activation; Regulation; Research; Resolution; Role; Satiation; Shapes; Signal Transduction; Site; Source; Stereotyped Behavior; Stereotyping; Stream; Structure; Synapses; System; Tachykinin; Taste Perception; Techniques; Technology; Testing; Toxin; Water; adipokinetic hormone; analog; connectome; corpus cardiacum; experimental study; feeding; fly; food quality; in vivo; interest; model organism; mutant; neural; neural network; neuromechanism; neuropeptide F; neuroregulation; postsynaptic neurons; receptor; receptor expression; reduced food intake; response; sugar; tool

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.

喂养是一种基本行为，严格调节以准确满足动物的代谢需求。 动物必须就食物做出的主要决定是摄取还是拒绝食物。物质 摄入了高营养价值，而毒素和有害物质被拒绝。为了做出这个决定， 该动物依靠其品味感来评估食物的质量。大多数动物都会回应甜蜜和 具有不同刻板印象的苦味剂：甜美的物质，通常富含卡路里，是食欲的， 接受的，虽然通常有害的苦涩的化合物被拒绝和避免。另一个重要部分 决定是摄取还是拒绝潜在食物是动物的代谢需求 饥饿与饱腹感之间的平衡。动物内部状态的这一方面通过 各种激素和神经调节剂之间的复杂平衡，有些是饥饿的信号 饱腹感。各种激素和神经调节剂的共同作用如何影响喂养 喂养行为的失调导致肥胖症或营养不良及其相关的兴趣很大 病态。 在此提案中，我们专注于果蝇中神经调节神经元的一个网络，其中神经调节剂 称为白曲霉素是由网络中的某些神经元分泌的，并由其他人检测到。我们 提出测试神经调节神经元的白素蛋白网络的假设整合了信息 关于味道质量和飞行的内部状态，以调节进食行为。在这个网络中，一组 神经元收到另外两个的输入：来自一个的口味信息，以及有关内部状态的信息 另一个动物。接收者神经元整合了两个信息流，然后调制 通过分泌调节喂养的其他神经肽来喂养行为。为了检验这一假设，我们使用 多收益的方法，包括解剖，功能和行为分析。在我们提出的研究中，我们 使用艺术技术来标记神经元连接性并操纵选择性子集的活性 神经元检查这些操纵的行为和功能效应。我们还开发了一个新的 研究神经调节部位的技术。该技术可实现选择性，无偏见的脑部 检查具有细胞分辨率的特定调节剂神经调节位点。因此，我们的研究将 加深我们对喂养调节的理解，并提供研究神经调节的新工具，一个 随着更多模型生物的神经连通图的重要性将增加重要性的研究领域 可用的。