High-resolution synaptic and functional connectivity mapping of a neural circuit architecture underlying a behavioral sequence

通过组装动作序列来产生复杂运动行为的能力对于 有目的的行动和生存。大脑中被认为驱动这种运动选择的区域的缺陷可能导致 行为变得异常重复（例如自闭症谱系障碍）。然而，神经回路结构 神经系统基本功能的基础仍然知之甚少。一个中心模型， 一种能够解释运动如何组合成序列的神经回路结构已经出现 来自多个物种的研究。在这种架构中，所有的动作都是并行准备的。运动 然后通过分层抑制来选择序列中的运动， 后来的人。先前的研究无法解释该模型如何从神经元连接中产生 和活动，部分原因是啮齿动物模型中神经回路的压倒性复杂性。我们建议 通过解剖身体梳理动作背后的神经回路来克服这个障碍 在果蝇，黑腹果蝇中。果蝇在复杂性和 他们表现出丰富的行为技能，而他们的大脑在数字上是紧凑的， 独特可识别的神经元，其活动可以使用强大的基于遗传的技术可视化和操纵 技术.疏导是探测运动序列的电路原理的理想选择，因为它由一个 可预测的一系列不同的运动。使用这个系统，我们以前表明，果蝇 梳理序列具有并行模型的特征，并建立了工具和 方法来剖析模型的电路基础。本提案的目的是定义神经系统如何 电路突触的连接和活动准备的不同运动并行，然后产生层次 抑制，平行模型预测的两个基本机制。在目标1中，我们将定义 电路被组织成使得运动能够并行地准备好。在目标2中，我们将阐明如何 分层抑制控制梳理移动选择。这些目标将有助于第一个 通过分层抑制产生顺序行为的神经电路架构的描述。等 架构不仅被提议为包括人类在内的物种之间的运动序列的基础，而且可以 还提供了一种通用机制，通过该机制，可以集成竞争的并行输入， 输出.因此，我们提出的果蝇研究将与其他动物相关，无论是为了了解如何 产生复杂的运动行为，并了解神经回路的组织和功能， 大致上

The ability to generate complex motor behaviors by assembling sequences of movements is essential for purposeful actions and survival. Defects in the brain regions thought to drive such movement selection can lead to behaviors becoming abnormally repetitive (e.g. autism spectrum disorder). Yet, the neural circuit architectures that underlie this fundamental function of the nervous system remain poorly understood. A central model of a neural circuit architecture that can account for how movements are assembled into sequences has emerged from studies across multiple species. In this architecture, all movements are readied in parallel. Movements within the sequence are then selected through hierarchical suppression, whereby earlier movements suppress later ones. Prior studies have been unable to decipher how the model might arise from neuronal connectivity and activity, in part due to the overwhelming complexity of neural circuitry in rodent models. We propose to overcome this barrier through dissection of the neural circuitry underlying sequential body grooming movements in the fruit fly, Drosophila melanogaster. Drosophila offer a useful compromise between complexity and tractability as they display a rich behavioral repertoire, while their brains are numerically compact and have uniquely identifiable neurons whose activity can be visualized and manipulated using powerful genetic-based techniques. Grooming is ideal for probing the circuit principles of movement sequences because it consists of a predictable sequence of distinct movements. Using this system, we previously showed that the Drosophila grooming sequence has the hallmarks of a parallel model, and established an infrastructure of tools and approaches to dissect the circuit basis of the model. The objective of this proposal is to define how the neural circuit synaptic connectivity and activity ready the different movements in parallel and then produce hierarchical suppression, two fundamental mechanisms predicted by the parallel model. In Aim 1, we will define how the circuitry is organized to enable the movements to be readied in parallel. In Aim 2, we will elucidate how hierarchical suppression controls grooming movement selection. These Aims will contribute to the first description of a neural circuit architecture that produces sequential behavior via hierarchical suppression. Such architectures are not only proposed to underlie movement sequences across species including humans, but can also provide a general mechanism by which competing parallel inputs can be integrated to produce a prioritized output. Thus, our proposed study in the fruit fly will be relevant to other animals, both for understanding how complex motor behaviors are produced and for understanding neural circuit organization and function more broadly.