Molecular and cellular determinants of Drosophila larva thermotaxis

果蝇幼虫趋热性的分子和细胞决定因素

• 批准号: 10334428
• 负责人: Paul Garrity
• 金额: $ 53.23万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10334428
• 关键词: Address; Affect; Anatomy; Animals; Area; Automobile Driving; Behavior; Behavioral; Brain; Brain region; Cells; Chemicals; Collaborations; Complex; Cues; Data; Dorsal; Drosophila genus; Elements; Family; Genetic; Goals; Image; Individual; Interneuron function; Interneurons; Investigation; Larva; Lobe; Maps; Mediating; Modality; Molecular; Molecular Genetics; Nervous system structure; Neurons; Neurosciences; Odors; Olfactory Pathways; Organ; Output; Peripheral; Physiological; Physiology; Process; Property; Research Personnel; Resolution; Role; Sensory; Shapes; Smell Perception; Stereotyped Behavior; Stimulus; Synapses; System; Taste Perception; Temperature; Testing; Texture; Thermoreceptors; Transducers; behavioral response; cognitive function; connectome; differential expression; feeding; flexibility; genetic manipulation; in vivo; in vivo imaging; information processing; insight; multilevel analysis; multisensory; mutant; neural circuit; receptor; response; sensor; sensory input; sensory integration; sensory mechanism; tool

Project Summary Molecular and cellular determinants of Drosophila larva thermotaxis How nervous systems detect and integrate multiple sensory cues to generate robust behaviors is a major question in neuroscience. Such integration is particularly salient in thermosensing, as animals are frequently required to integrate input from multiple thermoreceptor classes. Temperature's ubiquity also means input from other modalities (e.g., olfaction) is commonly received in the context of ongoing thermosensory stimulation. Achieving a comprehensive understanding of the molecular and circuit mechanisms underlying the integration of information from multiple sensors remains a challenge. We will address this challenge in the Drosophila larva. Its ease of genetic manipulation, synaptic-resolution connectome of thermosensory and olfactory processing areas, amenability to neuronal imaging, and stereotyped behaviors, all make it a favorable system for a comprehensive molecular and circuit level investigation of the mechanisms of sensory integration. We propose to achieve these goals in three aims: Aim 1) Establish the molecular and cellular receptors that provide thermosensory input In aims 1.a. and 1.b., we will identify the molecular basis of thermosensing by thermosensory neurons in the larval Dorsal Organ and examine their roles in guiding behavior through cell-specific inhibition and activation combined with high-resolution behavioral analysis. Aim 2) Probe the activities of the interneurons that process thermosensory input In aim 2.a., we will examine how thermosensory inputs act to modulate the neuronal activity of individually identifiable downstream projection neurons revealed from the larval antennal lobe connectome. This will establish the manner in which peripheral sensory input influences these second-order interneurons. In aim 2.b., we will investigate how thermosensory and olfactory systems interact in multi-sensory integration of chemical and thermal cues. Aim 3) Probe the functions of the interneurons that process thermosensory input In aim 3, we will determine the contribution of each projection neuron to thermotactic navigation through cell- specific inhibition and activation of individual PNs combined with high-resolution behavioral analysis. Taken together, these studies combine molecular genetics, physiology, and high resolution behavioral analyses to perform a comprehensive analysis of how this relatively small neural circuit processes multiple, distinct sensory inputs to control robust and flexible behaviors.

项目概要 果蝇幼虫趋热性的分子和细胞决定因素 神经系统如何检测和整合多种感觉线索以产生稳健的行为是一个主要问题 神经科学中的问题。这种整合在热传感中尤其重要，因为动物经常 需要整合来自多个温度感受器类别的输入。温度的普遍存在也意味着来自 其他方式（例如嗅觉）通常是在持续的热感觉刺激的背景下接受的。 全面了解集成背后的分子和电路机制 来自多个传感器的信息仍然是一个挑战。我们将在果蝇中应对这一挑战 幼虫。它易于基因操作，热觉和嗅觉的突触分辨率连接组 处理区域、神经元成像的适应性和刻板行为，所有这些都使其成为一个有利的系统 对感觉统合机制进行全面的分子和电路水平研究。我们 建议通过三个目标来实现这些目标： 目标 1) 建立提供热感输入的分子和细胞受体 在目标 1.a 中。 1.b.，我们将确定热感应神经元的热感应的分子基础 幼虫背器官并检查它们通过细胞特异性抑制和激活指导行为的作用 与高分辨率行为分析相结合。 目标 2) 探测处理热感输入的中间神经元的活动 在目标 2.a 中，我们将研究热感输入如何调节个体的神经元活动 从幼虫触角叶连接组中揭示出可识别的下游投射神经元。这将 建立外周感觉输入影响这些二阶中间神经元的方式。瞄准目标 2.b.，我们将研究热感觉和嗅觉系统如何在多感觉整合中相互作用 化学和热线索。 目标 3) 探究处理热感输入的中间神经元的功能 在目标 3 中，我们将通过细胞确定每个投射神经元对热定向导航的贡献 个体 PN 的特异性抑制和激活与高分辨率行为分析相结合。 总的来说，这些研究结合了分子遗传学、生理学和高分辨率行为学 分析对这个相对较小的神经回路如何处理多个、 不同的感官输入来控制稳健而灵活的行为。