Spinal cord neural circuits for left-right and flexor-extensor coordination

用于左右和屈伸肌协调的脊髓神经回路

• 批准号: 9118384
• 负责人: Martyn D Goulding
• 金额: $ 62.41万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9118384
• 关键词: Anatomy; Arts; Beds; Biological Models; Biological Neural Networks; Collaborations; Complement; Computer Simulation; Data; Development; Disabled Persons; Disease; Electrophysiology (science); Evaluation; Flexor; Generations; Genetic; Genetic Markers; Goals; Health; Image; In Vitro; Injury; Interneurons; Investigation; Ipsilateral; Label; Left; Locomotion; Methods; Modeling; Molecular Biology Techniques; Molecular Genetics; Monitor; Motor Activity; Movement; Mus; Neural Pathways; Neurons; Output; Pattern; Phase; Physiological; Play; Population; Role; Secure; Source; Speed; Spinal; Spinal Cord; Spinal Cord Diseases; Spinal cord injury; Study models; Swimming; Testing; Transgenic Mice; V1 neuron; V3 neuron; Walking; Work; base; central pattern generator; connectome; experience; in vivo; insight; interdisciplinary approach; locomotor control; motor function recovery; neural circuit; neuronal circuitry; neuroregulation; novel therapeutics; operation; relating to nervous system; research study; tool; transcription factor

DESCRIPTION (provided by applicant): Neuronal networks within the spinal cord organize and drive rhythmic movements like walking and swimming. These circuits represent the central pattern generator (CPG) that controls both the rhythm and the pattern of the locomotor activity. The organization of these circuits has recently begun to be revealed due to the state-of- art combination of complementary genetic, molecular and physiological methods. The overall goal of this project is to dissect the organization of the spinal CPG with focus on the organization of flexor-extensor alternating and left-right coordinating circuits. All work will be done on identifiable classes of spinal interneurons labeled by genetic markers in transgenic mice and/or classified by anatomic or electrophysiological labeling needed to obtain a unified picture of the CPG organization. We propose to identify the functional connectome and the interactions between these fundamental components of the CPG. The experiments performed will use a combination of electrophysiological, imaging, and molecular biology techniques complemented with advanced computer modeling. The three PIs involved in this project have strong background and experience in spinal cord studies and unique expertise in physiological, genetic and molecular methods (Martyn Goulding and Ole Kiehn) and computational modeling (Ilya Rybak). The Specific Aims of the project include: investigation of activity patterns and connectivity of the genetically identified spinal interneurons responsible for left-right coordinaton during locomotion (Aim 1), investigation of the genetically identified spinal interneurons and thei connectivity responsible for flexor-extensor alternation and their interactions with the circuits providing left-right coordination (Aim 2), development of a comprehensive computational model of spinal cord circuits (Aim 3). The proposed multidisciplinary approach based on the state-of-art methods and close collaboration between the three leading labs will investigate and analyze the specific contributions of left-right and flexor-extensor coordinating neuronal circuits and their interactions to the generation and control of the locomotor pattern and provide important insights into the neural organization of the mammalian spinal cord, leading to new strategies to treat spinal cord injury and degeneration spinal cord disorders.

描述（由申请人提供）：脊髓内的神经元网络组织并推动有节奏的运动，例如步行和游泳。这些电路代表中央模式发生器（CPG），它控制着运动活性的节奏和模式。由于互补遗传，分子和生理方法的最新结合，这些电路的组织最近开始揭示。该项目的总体目标是剖析脊柱CPG的组织，重点是屈伸器交替和左右协调电路的组织。所有工作都将在转基因小鼠中由遗传标记标记的可识别类脊柱中间神经元和/或通过解剖学或电生理标记进行分类，以获得CPG组织的统一图片。我们建议确定CPG的这些基本组件之间的功能连接组和相互作用。进行的实验将结合电生理，成像和分子生物学技术，辅以高级计算机建模。该项目所涉及的三个PI在脊髓研究中具有强大的背景和经验，并且在生理，遗传和分子方法（Martyn Goulding和Ole Kiehn）和计算建模（ILYA RYBAK）方面具有独特的专业知识。该项目的具体目的包括：对运动模式的调查和遗传识别的脊柱中间神经元的连通性，负责左右坐标的脊柱中间神经元（AIM 1）（AIM 1），对遗传性识别的脊柱中间神经元和遗传识别的连接性的调查，负责屈伸器交替及其与左旋的循环循环（目标均可互动）（目标2），目标是2） （目标3）。提出的基于最新方法和三个领先实验室之间的密切合作的多学科方法将调查和分析左右和屈伸器协调神经元电路的具体贡献，及其对自动者模式的产生和控制的相互作用，并为哺乳动物的神经组织提供重要的跨性别效果，以对哺乳动物的跨性别效应，从而导致了新策略，以培养新的策略，以培养新的策略，并将其引导。