Mapping the neural circuitry underlying walking

项目摘要 在整个动物王国里，走路是一种基本的、保守的行为。能够在移动中移动 协调、稳健而又灵活的方式对于动物在不断变化的环境中的生存至关重要。 运动行为是由大脑中的感觉神经纤维束控制的，这些神经纤维束与腹侧等运动中枢对话 胸腔内的神经索(VNC)执行精确的运动输出。下行神经元是主要的通道 在大脑和VNC之间实现这种连接的信息。然而，下游 精确控制特定类型肢体电机执行的靶神经元和复杂电路 诸如跑步、转弯、减速、切换步态、攀登、踏步等输出保持独立 未定义。这个项目的目的是绘制这些控制不同行走运动学的单独电路。在目标1中， 我们将使用一种名为Trans的转标技术来映射下行神经元的突触后目标 探戈。我们已经从以前的研究中了解到，所有下行的 果蝇的神经元，这种神经元的目标是腹神经索中的腿部神经毛。这些下降的 神经元很可能直接参与控制行走行为。另外，我们还有 有关域名系统子集的广泛行为信息。利用现有的形态和行为数据， 我们可以开始绘制出这些域名下游的电机和前置电机电路，并揭示 控制特定行走运动学的独特电路组件。我们计划筛选的一些域名会受到影响 因此，揭示它们是否会聚到相似或不同的目标上将是一件有趣的事情。在……里面 第二个目标，我们的目标是使用一种计算方法来搜索一代Gal4线，它的神经元 表达模式与我们想要研究的下游靶神经元相匹配。现有的拆分Gal4线路将是 将产生已识别的或新的神经元，以便获得对下游回路神经元的遗传访问 利息。在第三个目标中，我们将使用三个行为设置：飞行者、竞技场和飞球设置来 使用光遗传学交叉策略研究一系列高分辨率的行走参数。我们将使用 光遗传激活、沉默以及上位性实验，以绘制出电路的哪些组件 对于特定的行走运动学来说是充分的或必要的。

Project Summary Walking is an essential and conserved behavior across the animal kingdom. The ability to move in a coordinated, robust yet flexible manner is a crucial for an animal’s survival in the ever changing environment. Motor behaviors are controlled by sensory neuropils in the brain which talk to motor centers such as the ventral nerve cord (VNC) in the thorax to execute precise motor outputs. Descending neurons are the primary conduits of information that accomplish this connection between the brain and the VNC. However the downstream target neurons and complex circuits that precisely govern the execution of a specific kind of limbed motor output such as running, turning, slowing down, switching gait, climbing, stepping etc remain individually undefined. This project aims to map these individual circuits that control different walking kinematics. In aim 1, we will map the post-synaptic targets of descending neurons using a translabeling technique called Trans Tango. We already know from previous studies that have characterized the morphology of all the descending neurons in Drosophila, which DNs target the leg neuropils in the ventral nerve chord. These descending neurons are very likely to be directly implicated in controlling walking behavior. Additionally, we also have broad behavioral information for a subset of the DNs. Using this existing morphological and behavioral data, we can start to map out the motor and premotor circuits that are downstream of these DNs and reveal the distinct circuit components that control specific walking kinematics. Some of the DNs we plan to screen, affect similar behaviors hence it will be interesting to reveal whether they converge onto similar or different targets. In the second aim, we aim to use a computational approach search for generation Gal4 lines whose neuronal expression patterns match the downstream target neurons we want to study. Existing split Gal4 lines will be identified or new ones will be generated in order to gain genetic access to the downstream circuit neurons of interest. In the third aim, we will use three behavior setups: Flywalker, the Arena and the fly-on-ball setup to study a range of walking parameters in high resolution using optogenetics intersectional strategies. We will use optogenetic activation, silencing and also epistasis experiments to map out which components of the circuit are sufficient or necessary for a particular walking kinematic.