后肢
脊髓
神经科学
脊髓损伤
病变
抑制性突触后电位
兴奋性突触后电位
中心图形发生器
医学
腰脊髓
生物
解剖
病理
内科学
节奏
作者
Benedikt Brommer,Miao He,Zicong Zhang,Zhiyun Yang,Hang-Eun Joe,Junfeng Su,Yu Zhang,Jun‐Jie Zhu,Emilia Gouy,Jing Tang,Paul R. Williams,Wei Dai,Qi Wang,Ryan Solinsky,Bin Chen,Zhigang He
标识
DOI:10.1038/s41467-021-20980-4
摘要
Abstract After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.
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