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

该提案的目标是阐明视觉系统进行的神经计算，以识别即将发生的威胁及其用于生成避碰行为。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。实验数据将总结在一个生物物理模型的神经电路产生碰撞避免行为，将使用在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做出反应的理解。从该项目中获得的知识预计将允许未来设计高效的、神经启发的防撞系统。 拟议的实验将在果蝇果蝇中进行，果蝇是一个模型系统，其中提供了复杂的遗传学工具，包括遗传编码的Ca 2+指标和可以在特定神经亚群中表达的神经活动修饰剂。这些工具，配合最近的解剖学描述的视觉通路在电子显微镜水平，提供了研究神经元网络如何处理信息，导致视觉引导的逃避行为在一个前所未有的细节水平的可能性。特别地，这些工具将允许（1）进行行为实验，其中属于视觉引导的逃逸通路的特定神经元群体被沉默;（2）进行成像实验，允许研究属于视觉引导的逃逸通路的神经元在视觉系统的所有连续阶段的激活，并确定如何/何时出现对隐现刺激的特异性;（3）应用局部刺激和先进的微刺激技术，允许分离单个光感受器对与单个神经元中的隐现刺激相关的视觉信息的处理的贡献;（4）开发遗传工具，其允许通过使用新的阴离子通道视紫红质来沉默神经元群体，并且允许在两个连续阶段稀疏地标记该途径的神经元，或者用神经元活动的指示剂或者用光遗传学激活剂;（5）使用这些工具结合三维随机访问成像来测试在通路的连续阶段的功能连接性;以及（6）对沿着沿着视觉引导的逃逸通路进行的神经计算进行建模。

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.