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

通过组合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。被认为驱动这种运动选择的大脑区域的缺陷可能会导致 行为变得异常重复(例如自闭症谱系障碍)。然而，神经电路架构 神经系统这一基本功能的基础仍然知之甚少。的中心模型 能够解释运动如何组装成序列的神经电路体系结构已经出现 来自多个物种的研究。在这个架构中，所有动作都是并行准备的。动向 然后通过层级抑制来选择序列内的运动，从而抑制较早的运动 后来的。以前的研究一直无法破译这种模型是如何从神经元连接中产生的 和活动性，部分原因是啮齿动物模型中神经电路的压倒性复杂性。我们建议 通过解剖连续的身体梳理动作背后的神经回路来克服这一障碍 在果蝇中，果蝇黑腹果蝇。果蝇在复杂性和复杂性之间提供了有用的折衷方案 易驯服，因为他们表现出丰富的行为技能，而他们的大脑在数字上紧凑， 唯一可识别的神经元，其活动可以使用强大的基于基因的可视化和操纵 技巧。梳理是探索动作序列的电路原理的理想选择，因为它包含一个 可预测的不同动作序列。使用这个系统，我们之前展示了果蝇 梳理序列具有并行模式的特征，并建立了工具和 对模型的电路基础进行了剖析。这项提议的目标是定义神经是如何 回路突触的连通性和活动为不同的并行运动做好准备，然后产生层次化 抑制，这是并行模型预测的两种基本机制。在目标1中，我们将定义 电路被组织起来，以使运动能够并行准备。在目标2中，我们将阐明如何 分层抑制控制疏导运动选择。这些目标将有助于实现第一个目标 对通过分层抑制产生顺序行为的神经电路体系结构的描述。是这样的 建筑不仅被认为是包括人类在内的跨物种运动序列的基础，而且还可以 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以产生按优先顺序排列的 输出。因此，我们对果蝇的拟议研究将与其他动物相关，两者都有助于理解 产生复杂的运动行为，以便更多地了解神经电路的组织和功能 大体上说。

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.