Spinal Circuits for the Control of Dextrous Movement

项目总结：总体 脊髓内的局部网络代表了控制肢体驱动的基本计算层 运动行为，整合下行和感觉输入，以协调灵活的运动输出。意义重大 在确定发展方案的特征方面取得了进展，这些方案具体说明了核心基数 组成这些运动网络的中间神经元类型。这一知识已经被用来开发出一组 用于脊髓环路解剖和功能解剖的小鼠遗传试剂。到目前为止，这些遗传工具已经 主要用于研究腰椎脊髓的运动和脊椎反射。考虑到更广泛的 颈部回路产生的灵巧运动行为以及对这些行为的更多监督 通过下行运动通路，小鼠颈脊髓提供了一种独特的、易驯服的哺乳动物 用于了解本地运动网络如何产生协调运动以及如何产生协调运动的模型系统 这些运动行为是由大脑调节的。这支U19团队的总体目标--研究脑电路 方案建议包括两个方面：1)生成可伸缩的、高分辨率的前肢前置电机图谱 颈髓中的中间神经元，描述它们的连接性，分子表型， 电生理特性，以及对前肢行为的功能贡献，以及2) 描述导致肢体控制的网络交互的可测试预测神经模型。这个 根据实际行为结果和详细信息对这些电路进行功能询问和建模 有关生成这些行为的单元格类型的信息，将确保整个项目大于 各部分的总和。具体地说，研究计划将解决两个主要问题：1)节奏是如何 脊髓网络控制非节律性运动，这代表了大多数前肢运动行为，以及 2)如何修改这些脊椎回路以控制更复杂的关节运动，以实现前肢灵活性？ 为了解决这些问题，脊髓电路小组(TeamSCC)将产生：(A)前置马达 神经元间连接体，包括细胞位置和突触权重的信息，(B)a 遗传不同神经元生理特性和分子同一性的综合指数 每个主要中间神经元类别内的亚型，(C)自然脊神经回路控制的功能描述 前肢电机行为，以及(D)电机网络的工作模型，该模型描述电路连接如何 动力学产生了前肢行为的关键要素。最终，这些数据将被用来生成 基于Web的可搜索门户，具有链接到分子、电生理、功能、 和网络模型数据库。共同努力，这项工作将导致对本组织和 颈部电路的功能，这对正在努力解决如何运动的问题的团体来说将是非常有价值的 大脑中的中枢与脊髓中的感觉运动神经回路进行通信，以控制运动。

Project Summary: Overall Local networks within the spinal cord represent an essential computational layer for the control of limb-driven motor behaviors, integrating descending and sensory inputs to coordinate dexterous motor output. Significant advances have been made in characterizing the developmental programs that specify the core cardinal interneuron types that make up these motor networks. This knowledge has been used to develop a battery of mouse genetic reagents for spinal circuit anatomical and functional dissection. To date, these genetic tools have been primarily used to study locomotion and spinal reflexes in the lumbar spinal cord. Given the wider range of dexterous motor behaviors that are produced by cervical circuits and the increased oversight of these behaviors by descending motor pathways, the mouse cervical spinal cord provides a unique and tractable mammalian model system for understanding how coordinated movements are generated by local motor networks and how these motor behaviors are regulated by the brain. The overall goal of this U19 Team-Research BRAIN Circuit Program proposal is two-fold: 1) the generation of a scalable, high-resolution atlas of forelimb-premotor interneurons in the cervical spinal cord that describes their connectivity, molecular phenotypes, electrophysiological properties, and functional contributions to forelimb behaviors, and 2) the development of testable predictive neural models that describe the network interactions that give rise to limb control. The functional interrogation and modeling of these circuits, based on real behavioral outcomes and detailed information about the cell types that generate these behaviors, will ensure that the overall project is greater than the sum of its parts. Specifically, the research plan will address two overarching questions: 1) How do rhythmic spinal networks control non-rhythmic movements, which represent the majority of forelimb motor behaviors, and 2) How are these spinal circuits modified to control more complex joint movements to achieve forelimb dexterity? To address these questions, the Spinal Cord Circuit Team (TeamSCC) will generate: (a) a pre-motor interneuron connectome that includes information on cell positions and synaptic weightings, (b) a comprehensive index of the physiological properties and molecular identities of genetically distinct neuronal subtypes within each cardinal interneuron class, (c) a functional description of spinal circuit control of natural forelimb motor behaviors, and (d) a working model of the motor network that describes how circuit connectivity and dynamics give rise to key elements of forelimb behavior. Ultimately, these data will be used to generate a searchable web-based portal with 3D visualization tools linked to the molecular, electrophysiological, functional, and network model databases. Together, this work will lead to a deeper understanding of the organization and function of cervical circuitry, which will be of great value to groups that are grappling with the issue of how motor centers in the brain communicate with sensorimotor circuits in the spinal cord to control movement.