RP 1: Modeling Forelimb Motor Circuit Organization and Function

RP 1：前肢运动电路组织和功能建模

• 批准号: 10011918
• 负责人: Tatyana O. SHARPEE
• 金额: $ 28.14万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011918
• 关键词: Address; Affect; Architecture; Behavior; Behavioral; Brain; Cervical; Cervical spinal cord structure; Computational Technique; Computer Analysis; Coupled; Data; Elbow; Electrophysiology (science); Elements; Extensor; Fire - disasters; Flexor; Forelimb; Freedom; Future; Goals; Hodgkin-Huxley model; Interneurons; Investigation; Isometric Exercise; Isotonic Exercise; Joints; Kinetics; Limb structure; Measurement; Measures; Mechanics; Modeling; Molecular; Motor; Motor Activity; Motor Neurons; Motor output; Movement; Mus; Muscle; Neuromechanics; Neurons; Output; Pattern; Periodicity; Positioning Attribute; Property; Psychological Techniques; Public Domains; Research Project Grants; Signal Transduction; Slice; Source Code; Spinal; Spinal Cord; Testing; Time; Work; Wrist; base; cell type; central pattern generator; data sharing networks; excitatory neuron; experimental analysis; experimental study; in vivo; inhibitory neuron; joint mobilization; kinematics; limb movement; motor behavior; network models; neural circuit; neuronal circuitry; recruit; repository; response; simulation

Project Summary: Project 1 – Modeling Forelimb Motor Circuit Organization and Function This Research Project addresses the dynamics of motor circuits in the cervical spinal cord. Aims in this project will analyze how cervical spinal networks coordinate forelimb movement during rhythmic and non-rhythmic activity. The model will include neuronal elements (excitatory and inhibitory pre-motor neurons and antagonist pools of motor neurons), antagonist pairs of muscles, and mechanical components of the limb. Theoretical and computational techniques will be used to describe how these elements interact, including possible responses to descending brain commands, to generate forelimb activities such as isometric and isotonic movements. The first goal will be to compute how cervical spinal motor neurons fire in response to inputs (based on slice electrophysiology experiments, Projects 2 and 3), and how their firing is converted to muscle force (based on EMG recordings, Project 4). A second goal will be to analyze circuit configurations that achieve maximum control in order and predict new functional cell types that may be present in the spinal cord. Network models composed of motor and pre-motor neurons will then be constructed, defining the patterns of network firing and bursting of antagonistic motor pools, corresponding to elbow and wrist movements and static states. The model will be constrained by connectivity data (Project 2), and informed by theoretical analyses of optimal circuit configurations. Finally, a mechanical model of the limb will be connected to the neuronal model to generate a coherent picture of the transformation from descending input to the cervical spinal cord to limb movements. The dynamical responses of the model will be compared with the behavioral and in vivo electrophysiological data collected in Project 4. Overall, the theoretical analyses performed here, together with experimental investigations from Projects 2-4, will help inform general principles concerning how multiple neuronal types coordinate their response properties to achieve robust control of multiple dynamical variables.

项目概要：项目1 -前肢运动电路组织和功能建模 本研究计画探讨颈髓运动回路的动力学。本项目的目标 将分析颈椎网络如何协调前肢运动在节奏和非节奏 活动该模型将包括神经元元素（兴奋性和抑制性运动前神经元和拮抗剂） 运动神经元池）、拮抗肌对和肢体的机械组件。理论和 计算技术将被用来描述这些元素如何相互作用，包括可能的反应， 下行大脑命令，以产生前肢活动，如等距和等张运动。 第一个目标将是计算颈脊髓运动神经元如何响应输入而放电（基于切片 电生理学实验，项目2和3），以及它们的放电如何转化为肌肉力量（基于 EMG记录，项目4）。第二个目标是分析实现最大控制的电路配置 以便对脊髓中可能存在的新的功能细胞类型进行排序和预测。网络模型组成 运动神经元和前运动神经元的模型将被构建，定义网络放电和突发的模式。 对抗性运动池，对应于肘部和手腕的运动和静态。该车型将 受连通性数据（项目2）的约束，并通过最佳电路配置的理论分析获得信息。 最后，肢体的机械模型将连接到神经元模型以生成连贯的图片 从下行输入到颈髓到肢体运动的转换。动态 模型的反应将与在实验室中收集的行为和体内电生理数据进行比较。 项目4。总的来说，这里进行的理论分析，以及来自 项目2-4，将有助于告知关于多种神经元类型如何协调其反应的一般原则 属性，以实现多个动态变量的鲁棒控制。