Spinal cord injury induces serotonin supersensitivity without increasing intrinsic excitability of mouse V2a interneurons.
Spinal cord injury induces serotonin supersensitivity without increasing intrinsic excitability of mouse V2a interneurons.
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DOI：
10.1523/jneurosci.2995-12.2012
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发表时间：
2012-09-19
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影响因子：
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通讯作者：
Harris-Warrick RM
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作者：
Husch A;Van Patten GN;Hong DN;Scaperotti MM;Cramer N;Harris-Warrick RM
去神经诱导的塑性变化会损害脊髓损伤（SCI）后的运动恢复。 SCI 后脊髓运动神经元变得过度兴奋，但 SCI 后运动网络中间神经元的可塑性反应尚未研究。使用成年小鼠 SCI 模型，我们分析了完全脊髓损伤对小鼠腰椎 V2a 脊髓中间神经元内在电生理特性、兴奋性和对血清素 (5-HT) 的神经调节反应的影响，这有助于调节运动过程中的左右交替。 SCI 后 4 周，V2a 中间神经元的基线兴奋性或动作电位特性几乎没有变化；唯一改变的参数是降低的输入电阻。然而，V2a 中间神经元对 5-HT 的敏感性提高了 100-1000 倍。免疫细胞化学分析表明，SCI 导致血清素能纤维和 5-HT 转运蛋白 (SERT) 的协调损失。在完整小鼠中用西酞普兰阻断 SERT 并没有将 5-HT 敏感性提高到 SCI 后观察到的水平。 SCI 还引起 5-HT2C 受体簇数量和强度的增加，表明几种塑性变化协同增加 5-HT 敏感性。我们的结果表明，负责协调运动的脊髓神经元网络的不同组成部分受到 SCI 的不同影响，并强调在考虑针对功能恢复的治疗时了解这些变化的重要性。
Denervation induced plastic changes impair locomotor recovery after spinal cord injury (SCI). Spinal motoneurons become hyperexcitable after SCI, but the plastic responses of locomotor network interneurons after SCI have not been studied. Using an adult mouse SCI model, we analyzed the effects of complete spinal cord lesions on the intrinsic electrophysiological properties, excitability and neuromodulatory responses to serotonin (5-HT) in mouse lumbar V2a spinal interneurons, which help regulate left-right alternation during locomotion. Four weeks after SCI, V2a interneurons showed almost no changes in baseline excitability or action potential properties; the only parameter that changed was a reduced input resistance. However, V2a interneurons became 100-1000 fold more sensitive to 5-HT. Immunocytochemical analysis showed that SCI caused a coordinated loss of serotonergic fibers and the 5-HT transporter (SERT). Blocking the SERT with citalopram in intact mice did not increase 5-HT sensitivity to the level seen after SCI. SCI also evoked an increase in 5-HT2C receptor cluster number and intensity, suggesting that several plastic changes cooperate in increasing 5-HT sensitivity. Our results suggest that different components of the spinal neuronal network responsible for coordinating locomotion are differentially affected by SCI, and highlight the importance of understanding these changes when considering therapies targeted at functional recovery.