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

基本信息

批准号：
10132286
负责人：
KENTA ASAHINA
金额：
$ 41.23万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10132286
关键词：
Acetylcholine Address Affect Afferent Neurons Aggressive behavior Agonistic Behavior Alleles Ally Anatomy Animals Anxiety Arousal Behavior Behavioral Behavioral Mechanisms Biological Models Brain Cells Chemicals Choline Cues Data Defect Disease Dissection Drosophila genus Drosophila melanogaster Event FMRFamide Food Functional disorder Genetic Goals Human Hunger Knock-in Knowledge Lead Measures Mediating Mental disorders Modeling Molecular Morphology Nervous system structure Neuraxis Neuromodulator Neurons Neuropeptide Receptor Neuropeptides Neurotransmitters Pathology Peptide Synthesis Peptides Perception Pheromone Physiological Physiological Processes Physiology Plant Roots Play Population Process Reagent Research Resolution Role Sensory Signal Transduction Site Smell Perception Stimulus Study models Synapses System Tachykinin Tachykinin Receptor Taste Perception Testing Work base behavioral response combinatorial cost effective experimental study fast-acting neurotransmitter improved in vivo calcium imaging knowledge base male neural circuit neuronal circuitry neuropeptide F neuroregulation neurotransmitter release optogenetics receptor relating to nervous system reproductive response sensory stimulus success synergism tool vinegar fly

项目摘要

PROJECT SUMMARY Neuropeptides play important roles in modulating neural circuits that process olfactory and gustatory infor- mation. This modulation generally functions to align an animal's internal state (e.g., levels of arousal, or food status) with behavioral responses to sensory stimuli (e.g., pheromones or food-associated odorants). Although the neuropeptidergic modulation of specific sensory neurons has been described, the molecular and cellular mechanisms by which neuropeptides affect central chemosensory circuits are unknown. The long-term goal is to characterize the neuropeptidergic modulation of chemosensory circuits by deconstructing this physiological process into clearly defined, behaviorally relevant molecular and neuronal events. Importantly, altered chemosensation in humans is often associated with certain types of mental disorders, and characterizing at a molecular level the neuropeptidergic modulation of chemosensation is a fundamental first step toward under- standing and improving treatments for these disorders. The Drosophila model system offers an excellent plat- form for these studies, because neuropeptidergic systems can be precisely manipulated and the effects on well-characterized circuits mediating chemosensation-induced behaviors, such as male aggressive behavior, can be measured. Initial experiments will focus on the neuropeptide tachykinin, with the central hypothesis that neuropeptides act locally to affect a specific population of neurons to modulate chemosensory information rele- vant to male agonistic behavior. The three specific aims, each based on preliminary success, are to: 1) charac- terize the neuropeptidergic circuit that modulates pheromone-induced male agonistic behavior, 2) characterize synergies between neuropeptides and co-released neurotransmitters, and 3) elucidate the cellular basis of in- teractions among three neuropeptide (tachykinin, neuropeptide F and FMRFamide) that each modulate male agonistic behavior (a chemosensation-guided behavior). In Aim 1, neurons expressing the tachykinin receptor (Takr86C) will be morphologically characterized, and those receiving synaptic input from aggression-promoting tachykininergic neurons will be identified via photo-activatable GFP-assisted neuronal tracing and in vivo cal- cium imaging. In Aim 2, interactions between tachykinin and the co-expressed neurotransmitter acetylcholine will be characterized. Peptide or transmitter release will be independently blocked in relevant cells, and effects on downstream neuronal activity and behavior will be analyzed. In Aim 3, anatomical and physiological rela- tionships between neurons expressing tachykinin, neuropeptide F, or FMRFamide will be established, leading to a better understanding of how these three neuropeptides synergistically affect a pheromone-processing neu- ral circuit. Together, the research proposed here will uncover the genetic and cellular mechanisms by which neuropeptides physiologically affect chemosensory circuits to modulate behavior. Such knowledge will provide a fundamental understanding of how smell and taste perception is centrally controlled, and how dysfunction of this process may lead to non-adaptive responses to environmental cues.

项目概要神经肽在调节处理嗅觉和味觉信息的神经回路中发挥着重要作用。化。这种调节通常用于调整动物的内部状态（例如，唤醒水平或食物水平）状态）与对感官刺激（例如信息素或食物相关气味）的行为反应。虽然特定感觉神经元的神经肽能调节已经被描述，分子和细胞神经肽影响中枢化学感应回路的机制尚不清楚。长期目标是通过解构这种生理学来表征化学感应回路的神经肽能调节过程转化为明确定义的、行为相关的分子和神经元事件。重要的是，修改了人类的化学感觉通常与某些类型的精神障碍有关，其特征在于分子水平化学感觉的神经肽能调节是迈向低水平的基本第一步坚持并改进这些疾病的治疗方法。果蝇模型系统提供了一个优秀的平台这些研究的形式，因为神经肽能系统可以被精确操纵并且对介导化学感觉诱发行为的明确电路，例如男性攻击行为，可以测量。最初的实验将集中在神经肽速激肽上，其中心假设是神经肽局部作用，影响特定的神经元群，从而调节化学感应信息相关性有利于男性的竞争行为。这三个具体目标均以初步成功为基础，分别是：1）特征确定调节信息素诱导的男性竞争行为的神经肽能回路，2）表征神经肽和共同释放的神经递质之间的协同作用，以及3）阐明了in-的细胞基础三种神经肽（速激肽、神经肽 F 和 FMRFamide）之间的相互作用，每种神经肽均调节雄性竞争行为（化学感觉引导的行为）。在目标 1 中，表达速激肽受体的神经元（Takr86C）将进行形态学表征，并且那些接收来自促进攻击性的突触输入的速激能神经元将通过光激活 GFP 辅助神经元追踪和体内计算来识别 cium 成像。在目标 2 中，速激肽与共表达的神经递质乙酰胆碱之间的相互作用将被表征。肽或递质释放将在相关细胞中被独立阻断，并产生影响将分析下游神经元活动和行为。在目标 3 中，解剖学和生理学的关系表达速激肽、神经肽 F 或 FMRFamide 的神经元之间的关系将被建立，从而导致更好地理解这三种神经肽如何协同影响信息素处理神经元模拟电路。总之，这里提出的研究将揭示遗传和细胞机制神经肽在生理上影响化学感应回路以调节行为。这些知识将提供对嗅觉和味觉感知如何集中控制以及嗅觉和味觉功能障碍如何进行基本了解这个过程可能会导致对环境线索的非适应性反应。