Mechanisms of Motor Control in the Spinal Cord

脊髓运动控制机制

• 批准号: 10473623
• 负责人: Ariel Levine
• 金额: $ 224.55万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10473623
• 关键词: Adult; Area; Behavior; Behavioral; Biological; Biology; Brain; Cell Nucleus; Cells; Computer Analysis; Cues; Data; Data Analyses; Feedback; Foundations; Genes; Goals; Gold; In Situ; Knowledge; Link; Microglia; Molecular; Motor; Movement; Mus; Myelin; Neuraxis; Neurons; Pathway interactions; Patients; Population; Recovery; Reference Standards; Regenerative response; Regulation; Resources; Sensorimotor functions; Sensory; Spinal; Spinal Anesthesia; Spinal Cord; Spinal cord injury; Stroke; Techniques; Testing; Therapeutic Intervention; Tissues; Validation; Work; brain pathway; cell type; data sharing; improved; motor behavior; motor control; motor learning; mouse genetics; new therapeutic target; online resource; programs; recruit; relating to nervous system; single cell analysis; transcriptome sequencing

We seek to understand how the cells and circuits of the spinal cord encode neural programs for motor behavior. During this fiscal year, we made significant advances on two projects: (1) We established a gold standard reference of the cell types of the mouse spinal cord, using harmonized analysis of data from ten independent studies. Combined with high content in situ validation of dozens of marker genes, lineage analysis, and publicly available web resources to share this data, this work will serve as a foundational resource for spinal cord biology in the single cell era. In related work, we developed new computational analysis approaches for analyzing single cell data. (2) We used single cell techniques to track how each cell type in the spared tissue of the spinal cord changes following spinal cord injury. This work revealed two mechanisms of spontaneous recovery: a population of microglia that can be induced to phagocytose and clear myelin debris and a rare subset of neurons that, against the dogma in the field, represent central nervous system neurons that induce a molecular regeneration response. Both of these discoveries could provide new targets for therapeutic intervention.

我们试图了解脊髓的细胞和电路如何编码神经程序的运动行为。在这个财政年度，我们在两个项目上取得了重大进步： （1）我们使用十项独立研究的数据进行了协调的分析，我们建立了小鼠脊髓细胞类型的金标准参考。结合较高的含量验证数十种标记基因，谱系分析和公开可用的Web资源以共享此数据，这项工作将成为单细胞时代脊髓生物学的基础资源。在相关工作中，我们开发了用于分析单细胞数据的新计算分析方法。 （2）我们使用单细胞技术来跟踪脊髓损伤后脊髓损伤的较低组织中的每种细胞类型如何变化。这项工作揭示了两种自发恢复的机制：可引起吞噬和清除髓磷脂碎屑的小胶质细胞群，以及罕见的神经元子集，这些神经元与野外的教条代表了中枢神经系统神经元，可引起分子再生反应。这两个发现都可以为治疗干预提供新的目标。