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.

项目摘要 神经调节的核心功能之一是调整感官信息的内部表示 绳索与个人的内部状态。特别是，化学一致化可能具有截然不同的生物 - 逻辑含义取决于营养状态。例如，食物的气味不仅可以告知动物 食物在哪里，也有多么有价值。根据营养需求，动物使用感知的价值 食物作为调整与其他种族竞争水平的背景。而饥饿是已知的 通过神经调节改变嗅觉和味觉感觉神经元的检测阈值，如何 神经系统使用化学感应线索作为社会行为的上下文信息，在很大程度上仍然没有 已知。该研究计划的长期目标是表征 化学感应电路通过将这一生理过程解构为明确定义的，行为相关的 分子和神经元事件。果蝇果蝇Melanogaster是实现这一目标的理想选择。作为ge- 蝇可以通过网络处理模型生物体，可以精确控制具有定义行为的神经元种群 涉及神经调节的IORAL功能和基因。在上一个资金期间， 控制攻击行为的速度神经调节微电路具有全面特征 在分子水平和电路水平上iz。基于果蝇遗传学和社会行为的专业知识。 ior，拟议的项目将表征苍蝇神经系统如何使用肽基神经调节 将食物来源的气味转变为提示以调节侵略水平。三个特定目标，每个目标 通过成功的初步研究移植，是：（1）表征转换蛋白质的神经肽细胞 （2）表征分子和电路机制的赤字变化为化学刺激的变化。 Hugin神经调节，（3）确定介导食品驱动的Ag-的特定化学感应途径 gression。在AIM 1中，介导促进攻击行为的神经肽释放细胞 将识别出Tein不足的苍蝇，它们的编码营养状态的功能将在行为上是 特征。在AIM 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AIM 3中，特定类别的类别 检测从酵母发出的关键挥发性化合物的嗅觉感觉神经元，以及在 通过上述神经肽调节的嗅觉途径将被表征。结果 从提出的实验中将发现肽基神经调节在转化中的基本作用 - 将嗅觉信息纳入行为重要的环境环境中。神经调节对于 跨动物物种编码饥饿状态，以及许多参与饥饿控制的神经肽是避免的 保守。通过该项目获得的知识可能会导致对神经的更好理解 依赖于人类嗅觉感知的饥饿依赖性变化的基础。