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.

成人严重的脊髓损伤会导致病变下方不可逆的瘫痪。然而，在出生后刚接受完整胸部损伤的成年啮齿动物表现出熟练的后肢运动，而无需来自大脑的输入。脊髓如何达到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神经递质将空间定义的兴奋性中间神经元转换为抑制性表型，从而促进与运动神经元接触的突触的抑制。相比之下，新生儿脊髓损伤维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，模拟成人脊髓损伤后兴奋性中间神经元中观察到的抑制表型的基因操作消除了新生儿受伤小鼠的自主运动功能。相比之下，减弱这种抑制表型可以提高成人受伤后的运动能力。总之，这些数据表明，定义的兴奋性中间神经元的神经递质表型引导脊髓损伤后的运动恢复。