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 神经调节的中心功能之一是调节感觉信息的内部表征， 根据一个人的内部状态。特别是，化学感觉可以有显着不同的生物- 逻辑上的意义取决于营养状况。例如，食物的气味不仅能告诉动物 食物在哪里，还有它的价值根据营养需要，动物使用感知价值 食物作为一个背景来调整与其他同类的竞争水平。虽然饥饿是众所周知的， 通过神经调节改变嗅觉和味觉感觉神经元的检测阈值， 神经系统使用化学感觉线索作为社会行为的背景信息在很大程度上仍然是不可能的。 知道的这项研究计划的长期目标是描述神经肽能调节的特点， 化学感受回路，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Drosophila melanogaster是实现这一目标的理想选择。作为一名通用- 在遗传学上易于处理的模式生物中，果蝇允许精确控制具有定义的神经元数量， 与神经调节有关的免疫功能和基因。在上一个供资期间， 控制攻击性行为的速宁能神经调节微回路是全面表征的， 在分子和电路水平上实现了。基于我们在果蝇遗传学和社会学方面的专业知识， 或，拟议的项目将描述苍蝇神经系统如何使用肽能神经调节， 将食物产生的气味转化为调整攻击水平的线索。这三个具体目标，每一个都... 通过成功的初步研究，是：（1）表征神经肽能细胞， 化学刺激的改变表征的缺陷，（2）表征化学刺激的分子和电路机制， hugin神经调节，和（3）确定介导食物气味驱动的ag- 格雷辛。在目标1中，介导促进攻击行为的神经肽释放细胞在前- 将确定缺乏蛋白的果蝇，并从行为上研究它们编码营养状态的功能。 表征了在目标2中，神经肽及其同源受体在中肠和脑中的功能 将通过遗传学、生理学和行为学方法来表征。在目标3中， 嗅觉感觉神经元，检测从酵母释放的关键挥发性化合物，和神经节点， 将表征由上述神经肽调节的嗅觉通路。结果 将揭示肽能神经调节在转化中的基本作用， 将嗅觉信息融入到重要的行为环境中。神经调节对于 在动物物种中编码饥饿状态，许多参与饥饿控制的神经肽是进化的。 理性保守通过这个项目获得的知识可能会导致更好地理解神经 饥饿依赖性嗅觉变化的基础。