Genetic analysis of state-dependent chemosensory processing

状态依赖性化学感应处理的遗传分析

• 批准号: 10585464
• 负责人: Chih-Ying Su
• 金额: $ 43.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585464
• 关键词: Address; Amino Acid Transporter; Amino Acids; Animals; Aphrodisiacs; Assimilations; Behavior; Cells; Complex; Consumption; Cues; Data; Diet; Dietary Proteins; Drosophila genus; Energy Supply; Enteroendocrine Cell; Event; Exhibits; Family; Female; Food; Genetic; Hormones; Impairment; Individual; Ingestion; Instinct; Interoception; Intestines; Light; Logic; Macronutrients Nutrition; Mammals; Mediating; Messenger RNA; Modeling; Modernization; Molecular; Moods; Mothers; Names; Neurons; Neurophysiology - biologic function; Neurotransmitters; Nose; Nutrient; Olfactory Receptor Neurons; Outcome; Partner in relationship; Peptides; Peripheral; Pheromone; Physiological; Postpartum Period; Proteins; Publishing; Recovery; Regulation; Reproductive Behavior; Research; Role; Signal Pathway; Signal Transduction; Surveys; System; Testing; Time; Up-Regulation; building materials; detection of nutrient; dietary; experimental study; fly; genetic analysis; improved; innovation; insight; knock-down; member; neuroregulation; nutrition; peptide hormone; relating to nervous system; response; sensor; social; success; tool; transcriptome

PROJECT SUMMARY/ABSTRACT This proposal aims to determine how interoceptive nutrient detection modulates chemosensory responses and innate behavior. Protein-rich foods are widely considered beneficial to postpartum mothers by supplying energy and cellular building materials, or improving moods by acting as precursors for neurotransmitters. However, it remains unclear whether the nutrient’s restorative effect can also arise from other means: specifically, whether and how dietary amino acids can trigger signaling events to modulate neuronal function and behavior. To address these complex questions, it is necessary to dissociate the multifaceted functions of dietary proteins in neuromodulation or nutrition. Gut enteroendocrine cells, found in both flies and mammals, present excellent opportunities to address these questions, because these cells release peptide hormones in a nutrient-specific manner and, with modern genetic tools, can be specifically manipulated to release their hormones without ingestion of the nutrients. Using fruit flies as a model, this project leverages the powerful genetic toolkit and tractable nervous & gut enteroendocrine systems of D. melanogaster. Preliminary data showed that high-protein diet can accelerate receptivity recovery in mated females. At the molecular level, a subset of enteroendocrine cells exhibits heightened sensitivity to amino acids, thereby increasing the likelihood of releasing a specific peptide hormone from those cells upon protein ingestion. At the neuronal level, high-protein diet heightens the sensitivity of two types of olfactory receptor neurons (ORNs) to external social cues. Importantly, the specific gut-released peptide hormone is necessary for the ORN sensitization as well as the restorative effect of high protein on postmating receptivity. This proposal will test the hypothesis that mated females employ a “gut-to-nose” signaling pathway whereby dietary amino acids trigger the release of a peptide hormone from the gut to regulate sensitivity to social cues and restore critical innate behavior. The proposed experiments will characterize the regulation and function of the gut-released peptide hormone (Aim 1), identify the molecular mechanism by which the specific enteroendocrine cell subset responds to amino acids (Aim 2), and determine the role of peripheral chemosensory neuromodulation on receptivity recovery (Aim 3). The mechanistic insights expected from this research will shed light on how macronutrients impinge on particular internal physiological states to influence neuronal function and behavior—in a manner beyond nutrient assimilation or energy supply. Importantly, the proposed research reveals that nutrient responses of gut enteroendocrine cells can be modulated by mating status, and that the outcome of this modulated interoception (elevated release of a peptide hormone by dietary proteins) can in turn impact exteroception of social cues (ORNs’ sensitization to pheromones).

项目摘要/摘要 该提案旨在确定跨感受性营养检测如何调节化学水敏反应和 天生的行为。 和细胞建筑材料，或通过充当神经递质的前体来改善情绪。 仍然是叔叔，营养素的恢复效果是否也可能来自其他方式：具体而言，是否和 饮食中的氨基酸如何触发信号事件，以解决模块化的神经元功能和行为 复杂的问题，有必要辨别饮食蛋白在神经调节中的多方面功能 营养。 这些问题，因为这些细胞在营养特异性的Mannerner中rellse肽激素以及现代 可以专门操纵遗传工具以释放thormones而不会摄入营养。 水果苍蝇作为模型，该项目利用强大的遗传工具包和可拖动的神经和肠道内分泌 D. melanogaster的系统。 雌性在分子水平上 酸，从而增加了从蛋白质上从这些细胞中释放特定肽激素的可能性 摄取。在神经元水平上，高蛋白饮食增强了敏感 （ORN）对外部社会提示。 感官化作为高蛋白对延髓的恢复作用。 女性采用“肠道”信号传导途径的假设 肽激素从肠道释放到常规者对社会提示的敏感性并恢复了关键的先天性 行为。 激素（AIM 1），确定特定的肠内分泌细胞子群反应的分子机制 氨基酸（AIM 2），并确定周围化学敏感性神经调节在接受度恢复方面的作用 （AIM 3）。 特定的内部生理学状态以超越营养的方式影响神经元功能和行为-IN 大会或能源供应。 肠内分泌细胞可以通过交配状态调节，并且该模块化丙酸酯的结果 （通过饮食蛋白升高肽激素的释放）反过来影响社会提示的外部感（ORNS' 对信息素的感觉化）。