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脊髓兴奋性中间神经元通过神经递质表型转换调节脊髓损伤后的运动功能恢复。

Neurotransmitter phenotype switching by spinal excitatory interneurons regulates locomotor recovery after spinal cord injury.

机构信息

VIB-Neuroelectronics Research Flanders (NERF), Leuven, Belgium.

KU Leuven, Department of Neuroscience and Leuven Brain Institute, Leuven, Belgium.

出版信息

Nat Neurosci. 2022 May;25(5):617-629. doi: 10.1038/s41593-022-01067-9. Epub 2022 May 6.

DOI:10.1038/s41593-022-01067-9
PMID:35524138
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9076533/
Abstract

Severe spinal cord injury in adults leads to irreversible paralysis below the lesion. However, adult rodents that received a complete thoracic lesion just after birth demonstrate proficient hindlimb locomotion without input from the brain. How the spinal cord achieves such striking plasticity remains unknown. In this study, we found that adult spinal cord injury prompts neurotransmitter switching of spatially defined excitatory interneurons to an inhibitory phenotype, promoting inhibition at synapses contacting motor neurons. In contrast, neonatal spinal cord injury maintains the excitatory phenotype of glutamatergic interneurons and causes synaptic sprouting to facilitate excitation. Furthermore, genetic manipulation to mimic the inhibitory phenotype observed in excitatory interneurons after adult spinal cord injury abrogates autonomous locomotor functionality in neonatally injured mice. In comparison, attenuating this inhibitory phenotype improves locomotor capacity after adult injury. Together, these data demonstrate that neurotransmitter phenotype of defined excitatory interneurons steers locomotor recovery after spinal cord injury.

摘要

成人严重脊髓损伤导致损伤以下部位不可逆转的瘫痪。然而，出生后立即接受完全性胸段损伤的成年啮齿动物表现出无需大脑输入的熟练后肢运动能力。脊髓如何实现如此惊人的可塑性仍然未知。在这项研究中，我们发现成人脊髓损伤促使空间限定的兴奋性中间神经元的神经递质转换为抑制表型，促进与运动神经元接触的突触抑制。相比之下，新生儿脊髓损伤保持谷氨酸能中间神经元的兴奋性表型，并导致突触发芽以促进兴奋。此外，遗传操作模拟成年脊髓损伤后兴奋性中间神经元中观察到的抑制表型，可消除新生鼠损伤后自主运动功能。相比之下，减弱这种抑制表型可改善成年损伤后的运动能力。总之，这些数据表明，特定兴奋性中间神经元的神经递质表型决定了脊髓损伤后的运动恢复。

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