Peptidergic neuromodulation of microcircuits that control chemosensation-induced behaviors

控制化学感觉诱导行为的微电路肽能神经调节

• 批准号: 10668875
• 负责人: KENTA ASAHINA
• 金额: $ 51.16万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668875
• 关键词: Address; Afferent Neurons; Aggressive behavior; Animal Feed; Animals; Anxiety; Area; Behavior; Behavioral; Behavioral Paradigm; Biological; Brain; Cells; Central Nervous System; Chemicals; Cognitive; Communication; Complex; Cues; Detection; Drosophila genus; Drosophila melanogaster; Esthesia; Event; Exhibits; Experimental Genetics; Food; Funding; Genes; Genetic; Goals; Homologous Gene; Hormones; Human; Hunger; Individual; Knowledge; Mediating; Midgut; Modeling; Molecular; Motivation; National Institute on Deafness and Other Communication Disorders; Nervous System; Neurohormones; Neuromedin U; Neuromodulator; Neurons; Neuropeptides; Nutrient; Nutritional; Odors; Olfactory Pathways; Pathway interactions; Perception; Pheromone; Physiological; Physiological Processes; Physiology; Play; Population; Process; Proteins; Receptor Gene; Research; Resources; Role; Sensory; Shapes; Signal Transduction; Smell Perception; Social Behavior; Social Interaction; Source; Specific qualifier value; Stimulus; Strategic Planning; Taste Perception; Testing; Volatilization; Yeasts; behavioral response; brain cell; deprivation; experimental study; fly; male; model organism; neural; neuroregulation; novel; olfactory sensory neurons; olfactory threshold; programs; receptor; reproductive; response; sensory input; sensory stimulus; sensory system; small molecule; transmission process

PROJECT SUMMARY One of central functions of neuromodulation is to adjust the internal representations of sensory information ac- cording to the internal states of an individual. In particular, chemosensation can have dramatically different bio- logical meanings depending on the nutritional state. For instance, the smell of food not only informs an animal where the food is, but also how valuable it is. According to nutritional need, an animal uses the perceived value of the food as a context to adjust the level of competition with other conspecifics. While hunger is known to change the detection thresholds of olfactory and gustatory sensory neurons through neuromodulation, how the nervous system uses chemosensory cues as contextual information for social behaviors remains largely un- known. The long-term goal of this research program is to characterize the neuropeptidergic modulation of chemosensory circuits by deconstructing this physiological process into clearly defined, behaviorally relevant molecular and neuronal events. The fruit fly Drosophila melanogaster is ideal for achieving this goal. As a ge- netically tractable model organism, the fly allows precise control of neuronal populations with defined behav- ioral functions and genes involved in neuromodulation. During the previous funding period, the functions of tachyninergic neuromodulatory microcircuits that control aggressive behavior were comprehensively character- ized at the molecular and circuit levels. Building upon our expertise with Drosophila genetics and social behav- ior, the proposed project will characterize how the fly nervous system uses peptidergic neuromodulation to transform a food-derived odor into a cue to adjust the level of aggression. The three specific aims, each sup- ported by successful preliminary studies, are to: (1) characterize neuropeptidergic cells that convert protein deficit into altered representations of chemical stimuli, (2) characterize molecular and circuit mechanisms of hugin neuromodulation, and (3) determine specific chemosensory pathways that mediate food-odor-driven ag- gression. In Aim 1, the neuropeptide-releasing cells that mediate the promotion of aggressive behavior in pro- tein-deprived flies will be identified, and their function for encoding the nutritional state will be behaviorally characterized. In Aim 2, functions of neuropeptides and their cognate receptors in the midgut and in the brain will be characterized through genetic, physiological, and behavioral approaches. In Aim 3, the specific class of olfactory sensory neurons that detect key volatile compounds emitted from yeast, and the neural node in the olfactory pathway that are modulated by above-mentioned neuropeptides, will be characterized. The results from the proposed experiments will uncover the fundamental role of peptidergic neuromodulation in transform- ing olfactory information into a behaviorally important environmental context. Neuromodulation is important for encoding the hunger state across animal species, and many neuropeptides involved in hunger control are evo- lutionarily conserved. Knowledge obtained through this project may lead to a better understanding of the neural basis of hunger-dependent changes in olfactory perception in humans.

项目概要 神经调节的核心功能之一是调整感觉信息的内部表征 与个人的内在状态有关。特别是，化学感觉可以产生显着不同的生物效应 逻辑意义取决于营养状态。例如，食物的气味不仅告诉动物 食物在哪里，而且还有它的价值。根据营养需求，动物使用感知价值 食物作为背景来调整与其他同种的竞争水平。虽然众所周知饥饿 通过神经调节改变嗅觉和味觉感觉神经元的检测阈值， 神经系统使用化学感应线索作为社会行为的背景信息，但在很大程度上仍然不明确 已知。该研究计划的长期目标是表征神经肽能调节 通过将这种生理过程解构为明确定义的、行为相关的化学感应回路 分子和神经元事件。果蝇 Drosophila melanogaster 是实现这一目标的理想选择。作为一个 作为一种易于处理的模型生物体，苍蝇可以精确控制具有明确行为的神经元群体 口腔功能和参与神经调节的基因。在上一个资助期间，职能 控制攻击行为的速神经调节微电路具有全面的特征 在分子和电路水平上实现。基于我们在果蝇遗传学和社会行为方面的专业知识- 换句话说，拟议的项目将描述果蝇神经系统如何利用肽能神经调节来 将食物产生的气味转化为调整攻击性程度的提示。这三个具体目标，每一个都支持 通过成功的初步研究，目标是：（1）表征转化蛋白质的神经肽能细胞 缺乏化学刺激的改变表示，（2）表征化学刺激的分子和电路机制 Hugin 神经调节，以及（3）确定介导食物气味驱动的 ag- 的特定化学感应途径 侵略。在目标 1 中，神经肽释放细胞介导促进攻击性行为 将识别缺乏蛋白质的果蝇，并且它们编码营养状态的功能将在行为上 特点。在目标 2 中，神经肽及其同源受体在中肠和大脑中的功能 将通过遗传、生理和行为方法来表征。在目标 3 中，具体类别 嗅觉感觉神经元检测酵母散发的关键挥发性化合物，以及嗅觉神经节 将表征由上述神经肽调节的嗅觉通路。结果 从拟议的实验中将揭示肽能神经调节在转化中的基本作用 将嗅觉信息融入行为重要的环境背景中。神经调节对于以下方面很重要 编码跨动物物种的饥饿状态，许多参与饥饿控制的神经肽是进化而来的 进化保守的。通过这个项目获得的知识可能会有助于更好地理解神经网络 人类嗅觉的饥饿依赖性变化的基础。