Functional Development of Motor Networks

电机网络的功能开发

• 批准号: 8996723
• 负责人: David McLean
• 金额: $ 47.72万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8996723
• 关键词: Age; Axon; Biological Models; Cells; Complex; Consensus; Dendrites; Development; Disease; Ensure; Flexor; Genetic Identity; Goals; Health; Image; Inhibitory Synapse; Interneurons; Label; Left; Life; Limb structure; Location; Locomotion; Maps; Morphology; Motor; Motor Neurons; Movement; Mus; Muscle; Neurons; Occupations; Pattern; Population; Process; Recruitment Activity; Source; Speed; Spinal; Spinal Cord; Swimming; Synapses; Testing; Time; Variant; Ventral Roots; Vertebrates; Weight; Work; Zebrafish; driving behavior; in vivo; insight; motor disorder; motor neuron development; neuronal cell body; optogenetics; patch clamp; reconstitution; research study; zebrafish development

 DESCRIPTION (provided by applicant): Movements underlie all forms of vertebrate behavior and are driven by excitatory and inhibitory circuitry within the spinal cord. During locomotion, these networks generate rhythmic commands to motor neurons innervating muscles in the limbs and trunk. In all vertebrates, the motor neurons and their target musculature (motor units) are organized as functional synergists and antagonists. While excitatory circuits ensure the coordinated activation of functionally synergistic motor units, inhibitory circuits maintain the alternation of functionally antagonistic ones. As movements are generated with greater intensity, larger motor units that can exert greater force are recruited into the active pool in an orderly fashion that matches features related to their size, excitability and target musculature. However, regardless of intensity of locomotion, antagonistic motor units are typically activated in alternation. Despite decades of work studying the spinal inhibitory circuitry responsible for left-right or flexor-extensor alternation, relatively little is known about how inhibition is organized o ensure the appropriate activation of motor units of differing sizes during variations in movement speed or strength. Our goal is to determine the existence of systematic patterns of reciprocal inhibition that help coordinate the recruitment patterns of spinal motor neurons during locomotion using zebrafish as a model system. We will test the hypothesis that the strength of inhibitory synaptic connections arises in an orderly fashion during development and is mapped according to speed within motor neurons, such that inhibition at faster speeds arrives early and more proximally, while inhibition at slower speeds arrives later and more distally. The patterns we reveal here will provide critical mechanistic insight into the normal functional integration of inhibition and motor neuron excitability, disruptions of which underlie numerous motor diseases and disorders.

 描述（由申请人提供）：运动是所有形式的脊椎动物行为的基础，并由脊髓内的兴奋和抑制回路驱动。在运动过程中，这些网络向支配四肢和躯干肌肉的运动神经元发出有节奏的命令。在所有脊椎动物中，运动神经元和它们的目标肌肉组织（运动单位）被组织为功能协同剂和拮抗剂。兴奋性回路确保功能协同运动单元的协调激活，抑制性回路维持功能拮抗性回路的交替。随着运动产生的强度更大，可以施加更大力量的更大的运动单元以有序的方式被招募到活动池中，与它们的大小，兴奋性和目标肌肉组织相关的特征相匹配。然而，无论运动强度如何，对抗性运动单位通常会交替激活。尽管几十年来研究脊髓抑制回路负责左右或屈伸肌交替，相对较少的是知道如何组织抑制，以确保适当的激活不同大小的运动单位在运动速度或强度的变化。我们的目标是确定系统的相互抑制模式的存在，以斑马鱼为模型系统，帮助协调运动过程中脊髓运动神经元的招聘模式。我们将测试的假设，抑制性突触连接的强度出现在一个有序的方式在发展过程中，并根据运动神经元内的速度映射，这样的抑制在更快的速度到达早期和更近端，而抑制在较慢的速度到达较晚，更远。我们在这里揭示的模式将提供关键的机制洞察抑制和运动神经元兴奋性的正常功能整合，中断的基础上许多运动疾病和障碍。