Mechanisms of Motor Control in the Spinal Cord

脊髓运动控制机制

• 批准号: 10932764
• 负责人: Ariel Levine
• 金额: $ 251.38万
• 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/10932764
• 关键词: Adult; Area; Atlases; Behavior; Behavioral; Brain; Cell Size; Cell physiology; Cells; Central Nervous System; Contusions; Cues; Cytoskeleton; Disease; Feedback; Gene Expression Profile; Genes; Genetic; Genetic Predisposition to Disease; Goals; Human; Injury; Knowledge; Link; Mediating; Modeling; Motor; Motor Neurons; Movement; Mus; Natural History; Neurons; Pathway interactions; Patients; Population; Recovery; Regulation; Sensorimotor functions; Sensory; Spinal; Spinal Cord; Spinal cord injury; Stroke; Therapeutic Intervention; Time; Vertebral column; Viral; Work; brain pathway; cell type; excitatory neuron; improved; motor behavior; motor control; motor learning; mouse genetics; neural; neurological rehabilitation; new therapeutic target; programs; recruit; regenerative; response; single cell sequencing; single nucleus RNA-sequencing; tool

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 two major advances in our work. First, we characterized the cell-type specific responses to spinal cord injury. We examined the natural history time course of responses to a severe contusion injury, a translationally relevant model. We found rare spinal cord neurons that expressed a pro-regenerative gene expression signature, identified the major fraction of these neurons as spinocerebellar projection neurons, and showed that these neurons actually grow out after injury. We also analyzed how cell types respond to neuro-rehabilitation injury and helped to identify a population of ventral excitatory neurons that are crucial for mediating the effects of this powerful therapy. Both of these discoveries could provide new targets for therapeutic intervention. Second, we used single cell sequencing to profile the human spinal cord. We created the first atlas of neuronal diversity in the adult human cord and found that human motoneurons, that are vulnerable to degeneration in the disease ALS, are characterized by genes related to the cytoskeleton, cell size, and genetic predisposition to ALS itself.

我们试图了解脊髓的细胞和回路如何编码运动行为的神经程序。本财年，我们的工作取得了两项重大进展。首先，我们描述了细胞类型对脊髓损伤的特异性反应。我们检查了对严重挫伤反应的自然历史时间过程，这是一个翻译相关模型。我们发现表达促再生基因表达特征的罕见脊髓神经元，将这些神经元的主要部分鉴定为脊髓小脑投射神经元，并表明这些神经元实际上在损伤后生长。我们还分析了细胞类型如何响应神经康复损伤，并帮助识别腹侧兴奋性神经元群，这些神经元对于调节这种强大疗法的效果至关重要。这两项发现都可以为治疗干预提供新的目标。其次，我们使用单细胞测序来分析人类脊髓。我们创建了第一个成人脊髓神经元多样性图谱，发现人类运动神经元在 ALS 疾病中容易发生退化，其特征是与细胞骨架、细胞大小和 ALS 本身遗传易感性相关的基因。

项目成果

Graded Arrays of Spinal and Supraspinal V2a Interneuron Subtypes Underlie Forelimb and Hindlimb Motor Control.

• DOI: 10.1016/j.neuron.2018.01.023
• 发表时间: 2018-02-21
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Hayashi M;Hinckley CA;Driscoll SP;Moore NJ;Levine AJ;Hilde KL;Sharma K;Pfaff SL
• 通讯作者: Pfaff SL

Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons.

• DOI: 10.1038/s41467-022-33184-1
• 发表时间: 2022-09-26
• 期刊: Nature communications
• 影响因子: 16.6

Molecular and spatial profiling of the paraventricular nucleus of the thalamus.

• DOI: 10.7554/elife.81818
• 发表时间: 2023-03-03
• 期刊: eLife
• 影响因子: 7.7
• 作者: Gao C;Gohel CA;Leng Y;Ma J;Goldman D;Levine AJ;Penzo MA
• 通讯作者: Penzo MA

A spinoparabrachial circuit defined by Tacr1 expression drives pain.

• DOI: 10.7554/elife.61135
• 发表时间: 2021-02-16
• 期刊: eLife
• 影响因子: 7.7
• 作者: Barik A;Sathyamurthy A;Thompson J;Seltzer M;Levine A;Chesler A
• 通讯作者: Chesler A

A harmonized atlas of mouse spinal cord cell types and their spatial organization.

• DOI: 10.1038/s41467-021-25125-1
• 发表时间: 2021-09-29
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Russ DE;Cross RBP;Li L;Koch SC;Matson KJE;Yadav A;Alkaslasi MR;Lee DI;Le Pichon CE;Menon V;Levine AJ
• 通讯作者: Levine AJ