De novo establishment of circuit modules restores locomotion after spinal cord injury in adult zebrafish
De novo establishment of circuit modules restores locomotion after spinal cord injury in adult zebrafish
复制标题
从头建立电路模块可恢复成年斑马鱼脊髓损伤后的运动能力
DOI：
10.1016/j.celrep.2022.111535
复制
发表时间：
2022-10-25
期刊：
影响因子：
8.8
通讯作者：
Song, Jianren
中科院分区：
文献类型：
--
作者：
Huang, Chun-Xiao;Wang, Zhen;Song, Jianren
脊髓损伤（SCI）后自发性运动恢复的机制尚不清楚。研究人员利用完全脊髓损伤的成年斑马鱼，发现V2a中间神经元可以按照亚类特异性和时间顺序再生轴突，以桥接受损的脊髓节段。脊髓损伤后早期，单一的高节律动神经回路的重建仅由轴突再生的快速V2a中间神经元驱动。随后，重建的椎管内新生回路由轴突再生的快速和慢速V2a中间神经元组成模块化设计，分别选择性地驱动尾侧快速V2a/运动神经元和慢速V2a/运动神经元。这种有序的电路重建决定了运动功能的逐步恢复，并概括了发育过程。这一过程可因钙凝素（一种快速模块相关蛋白）的消融而中断，并可因体育训练而加速。这些发现表明，促进本体脊髓V2a中间神经元轴突再生和脊髓内新生回路的建立是脊髓损伤后体育训练有效性的基础。
Mechanisms underlying spontaneous locomotor recovery after spinal cord injury (SCI) remain unclear. Using adult zebrafish with complete SCI, we show that V2a interneurons regrow their axon to bridge the lesioned spinal segments in a subclass-specific and chronological order. Early after SCI, reestablishment of a unitary high-rhythm iocomotor circuit is driven merely by axon-regrown fast V2a interneurons. Later, the reestablished intraspinal de novo circuit is organized into a modular design by axon-regrown fast and slow V2a interneurons rostral to the lesion, selectively driving caudal fast V2a/motor neurons and slow V2a/motor neurons, respectively. This orderly circuitry reestablishment determines the stepwise restoration of locomotor repertoire and recapitulates developmental processes. This progress can be interrupted by ablation of calretinin, a fast module-related protein, and accelerated by physical training. These findings suggest that promotion of axon regrowth of propriospinal V2a interneurons and establishment of de novo intraspinal circuits underpin the effectiveness of physical training in patients after SCI.