CRCNS: Functional Dissection of a Looming-Sensitive Neural Pathway in Drosophila

该提案的目标是阐明由视觉系统进行的神经计算，以识别迫在眉睫的威胁及其用于产生避碰行为的用途。该提案将开发先进的遗传、行为和成像技术来解决这些问题。实验数据将总结为产生避碰行为的神经回路的生物物理模型，该模型将使用项目期间获得的实验数据进行验证。该项目将促进我们对视觉系统如何在自然视觉环境中可靠地识别威胁而不对无关的视觉刺激作出反应的理解。从该项目中获得的知识有望在未来设计出高效的、神经启发的避碰系统。提出的实验将在果蝇中进行，果蝇是一个模型系统，其中有复杂的遗传学工具，包括遗传编码的Ca2+指标和可以在特定神经亚群中表达的神经活动修饰因子。这些工具与最近在电子显微镜水平上对视觉通路的解剖描述相结合，为研究神经元网络如何处理导致视觉引导逃逸行为的信息提供了前所未有的细节水平。特别是，这些工具将允许(1)进行行为实验，其中属于视觉引导逃逸途径的特定神经元群体被沉默；(2)进行成像实验，研究视觉引导逃逸通路神经元在视觉系统所有连续阶段的激活情况，并确定对隐现刺激的特异性是如何/何时产生的；(3)应用局部刺激和先进的微刺激技术，分离单个光感受器对单个神经元中与隐现刺激相关的视觉信息处理的贡献；(4)开发遗传工具，通过使用新型阴离子通道视紫红质来沉默神经元群体，并允许在两个连续阶段稀疏标记该途径的神经元，要么使用神经元活性指标，要么使用光遗传激活剂；(5)结合三维随机成像，利用这些工具测试通路连续阶段的功能连通性；(6)模拟沿视觉引导逃离路径进行的神经计算。

The goal of the proposal is to elucidate the neural computations carried out by the visual system to identify an impending threat and their use for the generation of collision avoidance behaviors. The proposal will develop advanced genetic, behavioral and imaging techniques to address these questions. The experimental data will be summarized in a biophysical model of the neural circuits generating collision avoidance behaviors that will be validated using the experimental data acquired during the project. The project will advance our understanding of how the visual system goes about reliably identifying a threat in the natural visual environment without reacting to irrelevant visual stimuli. The knowledge gained from the project is expected to allow the future design of efficient, neurally-inspired collision avoidance systems. The proposed experiments will be carried out in the fruit fly Drosophila, a model system in which sophisticated genetics tools are available, including genetically encoded Ca2+ indicators and modifiers of neural activity that can be expressed in specific neural subpopulations. These tools, paired with the recent anatomical description of visual pathways at the electron microscopic level, offer the possibility of investigating how networks of neurons process information leading to visually guided escape behaviors at an unprecedented level of detail. In particular, these tools will allow (1) to carry out behavioral experiments where specific populations of neurons belonging to the visually-guided escape pathway are silenced; (2) to perform imaging experiments allowing to study the activation of the neurons belonging to the visually-guided escape pathway at all successive stages of the visual system and determine how/when the specificity for looming stimuli arises; (3) to apply localized stimuli and advanced microstimulation techniques allowing to isolate the contribution of individual photoreceptors to the processing of visual information related to looming stimuli in single neurons; (4) to develop genetic tools allowing to silence populations of neurons by using novel anion channel rhodopsins and allowing to sparsely label neurons of the pathway at two successive stages, either with an indicator of neuronal activity or with an optogenetic activator; (5) to test the functional connectivity at successive stages of the pathway using these tools in conjunction with three dimensional random access imaging; and (6) to model the neural computations carried out along the visually guided escape pathway.