Molecular and cellular determinants of Drosophila larva thermotaxis

项目摘要 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个感官线索以产生强健的行为是一个主要的 神经科学中的问题。这种集成在热敏传感器中尤其显著，因为动物经常 集成来自多个温度感应器类别的输入所需。温度的普遍存在也意味着来自 其他形式(例如，嗅觉)通常在正在进行的热觉刺激的背景下接受。 全面了解整合背后的分子和电路机制 从多个传感器获取信息仍然是一个挑战。我们将在果蝇中解决这一挑战 幼虫。它易于基因操作、突触分辨的温度感觉和嗅觉连接体 加工区，神经元成像的适应性，以及刻板的行为，这些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)建立提供热敏输入的分子和细胞受体 在AIMS 1.A.中和1.b.，我们将确定热感觉神经元在体温感觉的分子基础。 幼虫背部器官，并研究它们通过细胞特异性抑制和激活在指导行为中的作用 结合高分辨率的行为分析。 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，我们将研究温度感觉输入如何调节个体的神经元活动。 从幼虫触角叶连接体中发现可识别的下游投射神经元。这将是 确定外周感觉输入影响这些二级中间神经元的方式。在AIM 2.b.我们将研究温度感觉和嗅觉系统如何在多感觉整合中相互作用 化学和热信号。 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在细胞趋热导航中的作用。 结合高分辨率行为分析对个体三叉神经节的特异性抑制和激活。 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 分析以执行对这个相对较小的神经电路如何处理多个、 独特的感官输入，可控制强健灵活的行为。

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.