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.

项目摘要 果蝇幼虫趋热性的分子和细胞决定因子 神经系统如何检测和整合多种感官线索，以产生强大的行为是一个主要的 神经科学的问题这种整合在热敏中特别突出，因为动物经常 需要集成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 其它模态（例如，嗅觉）通常在持续的热感觉刺激的情况下接收。 实现对整合的分子和电路机制的全面理解 来自多个传感器的信息仍然是一个挑战。我们将在果蝇中解决这个挑战 幼虫其易于遗传操作，突触分辨连接体的温度和嗅觉 处理区域、对神经成像的顺从性和刻板的行为，都使它成为一个有利的系统 对感觉整合的机制进行全面的分子和电路水平的研究。我们 建议通过三个目标实现这些目标： 目的1）建立提供温度感觉输入的分子和细胞受体 在目标1.a中。和1.b.，我们将确定热感觉神经元的温度感觉的分子基础， 幼虫背部器官，并通过细胞特异性抑制和激活来检查它们在指导行为中的作用 结合高分辨率行为分析。 目的2）探讨处理温度感觉输入的中间神经元的活动 在目标2.a中，我们将研究热感觉输入如何调节个体的神经元活动， 可识别的下游投射神经元揭示了幼虫触角叶连接体。这将 建立外周感觉输入影响这些二级中间神经元的方式。在aim中 2.b.，我们将研究如何热敏和嗅觉系统相互作用的多感官整合， 化学和热线索。 目的3）探讨处理温度感觉输入的中间神经元的功能 在目标3中，我们将确定每个投射神经元对通过细胞的趋热导航的贡献。 结合高分辨率行为分析的单个PN的特异性抑制和激活。 总之，这些研究结合了联合收割机分子遗传学、生理学和高分辨率行为学。 分析来执行这个相对较小的神经回路如何处理多个， 不同的感官输入，以控制强大而灵活的行为。