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，受到严格监管，以精确满足动物的代谢需求。 动物对于食物必须做出的首要决定是摄入还是拒绝。物质 营养价值高的物质被摄入，毒素和有害物质被排除。为了做出这个决定， 动物依靠其味觉来评价食物的质量。大多数动物对甜食有反应 苦味促味剂具有不同的刻板行为：甜味物质，通常热量丰富，具有食欲和 接受，而通常有害的苦味化合物则被拒绝和避免。该计划的另一个重要部分 决定是否摄入或拒绝潜在的食物是动物的代谢需求，表现为 饥饿与饱足之间的平衡。动物内部状态的这个方面是通过以下方式进行评估的： 各种激素和神经调节剂之间错综复杂的平衡，一些信号发出饥饿信号，而另一些则发出信号 饱腹感。各种激素和神经调节剂的协同作用如何影响喂养是一个领域 喂养行为失调会导致肥胖或营养不良及其相关 发病率。 在这项提案中，我们重点关注果蝇中的一个神经调节神经元网络，其中神经调节剂 被称为白细胞激肽的神经元由网络内的某些神经元子集分泌并被其他神经元检测到。我们 提出检验神经调节神经元的白细胞激肽网络整合信息的假设 关于果蝇的味觉质量和内部状态来调节采食行为。在这个网络中，一组 神经元接收来自另外两个神经元的输入：来自一个神经元的味道信息以及有关内部状态的信息 动物与其他动物的区别。接收神经元整合两个信息流并依次调节 通过分泌其他调节摄食的神经肽来控制摄食行为。为了检验这个假设，我们使用 多管齐下的方法，包括解剖学、功能和行为分析。在我们提出的研究中，我们 使用最先进的技术来标记神经元连接并操纵选择性子集的活动 神经元来检查这些操作的行为和功能影响。我们还开发了一种新的 研究神经调节位点的技术。该技术能够实现选择性、公正、全脑 通过细胞分辨率检查特定调节剂的神经调节位点。因此，我们的研究将 加深我们对进食调节的理解，并为研究神经调节提供新工具， 随着更多模式生物的神经连接图变得越来越重要，该研究领域将变得越来越重要 可用的。