Pre-motor neural circuits enable versatile and sequential limb movements

前运动神经回路可实现多功能且连续的肢体运动

• 批准号: 10721086
• 负责人: JULIE H SIMPSON
• 金额: $ 217.31万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10721086
• 关键词: Abdomen; Anatomy; Animals; Architecture; BRAIN initiative; Basic Science; Behavior; Behavioral; Binding; Chest; Complex; Contralateral; Data; Data Set; Drosophila genus; Dust; Electron Microscopy; Elements; Elevator; Future; Genetic; Genetic Screening; Goals; Grooming; Guidelines; Head; Intervention; Joints; Leg; Limb structure; Logic; Maps; Measurable; Measurement; Measures; Mission; Modeling; Motor; Motor Neurons; Movement; Muscle; Nerve; Nervous System; Neuroanatomy; Neurons; Output; Pathway interactions; Pattern; RNA Interference; Reagent; Reproducibility; Research; Role; Services; Shapes; Swimming; Synapses; Testing; Time; United States National Institutes of Health; Vocabulary; Walking; Wing; Work; arm; classification algorithm; connectome; experimental study; flexibility; fly; gene therapy; inhibitory neuron; limb movement; motor control; neural; neural circuit; optogenetics; recruit; response; synergism; temporal measurement; tool

Abstract Movements are measurable outputs of the nervous system and simple movements can be combined to compose complicated behaviors. We use limb tracking and connectome analyses to map the neural circuits controlling the elemental leg movements in Drosophila grooming. The organization of the pre-motor networks for this innate, sequential behavior will show a successful solution for a complex motor control problem and reveal generalizable connectivity motifs whose computational functions can be experimentally tested. Starting from a detailed understanding of the temporal patterns in this behavior, we will identify the simplest movement subroutines that can be combined to assemble the whole repertoire. The circuits that produce these movements lie between the command-like neurons that initiate them and subsets of motor neurons that execute them. Using the results of our genetic screens for command neurons and new electron microscopy data for the Drosophila ventral nerve cord, we will trace neuronal connections to uncover the complete pre-motor network, showing which groups of muscles are bound to work together by common excitatory and inhibitory connections to their associated motor neurons. The pre-motor connectome allows us to test possible circuit functions through modeling. We will investigate whether command neurons that induce grooming sequences with shared movements converge onto common pre-motor nodes or maintain independent control pathways. By mapping inhibitory connections, we will determine whether these add flexibility to efficiently modify aspects of elemental movements: for example, if leg extension is a building block, it could be directed toward the head for a sweep or toward the contralateral leg for a rub by adding and subtracting a few additional motor neurons targeting more proximal elevator muscles. The anatomical connectome for pre-motor circuits constrains hypotheses about circuit function, leads to unexpected discoveries of highly connected nodes, and guides future experiments to measure neuronal activity and behavioral consequences.

抽象的 运动是神经系统可测量的输出，简单的运动可以 组合起来构成复杂的行为。我们使用肢体跟踪和 连接组分析以绘制控制基本腿的神经回路 果蝇梳理毛发的动作。为此目的运动前网络的组织 固有的顺序行为将展示复杂电机控制的成功解决方案 问题并揭示可推广的连接图案，其计算功能 可以通过实验进行测试。 从详细了解这种行为的时间模式开始，我们将 确定可以组合起来组装的最简单的运动子程序 全部曲目。产生这些运动的电路位于 启动它们的类似命令的神经元以及执行的运动神经元子集 他们。利用我们的基因筛选结果来寻找命令神经元和新电子 果蝇腹神经索的显微镜数据，我们将追踪神经元 连接以揭示完整的运动前网络，显示哪些组 肌肉必然通过共同的兴奋性和抑制性连接来协同工作 他们相关的运动神经元。 电机前连接组使我们能够通过建模来测试可能的电路功能。 我们将研究是否指挥神经元诱导梳理序列 共享运动会聚到共同的前运动节点或保持独立 控制途径。通过映射抑制连接，我们将确定这些是否 增加灵活性以有效地修改基本运动的各个方面：例如，如果腿 延伸是一个构建块，它可以指向头部进行扫掠或指向 通过添加和减去一些额外的运动神经元来摩擦对侧腿 针对更近端的电梯肌肉。运动前的解剖连接组 电路限制了关于电路功能的假设，导致了意想不到的发现 高度连接的节点，并指导未来测量神经元活动的实验 和行为后果。