Glutamate Transporters Regulate Lesion-Induced Plasticity in the Developing Somatosensory Cortex
Glutamate Transporters Regulate Lesion-Induced Plasticity in the Developing Somatosensory Cortex
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DOI：
10.1523/jneurosci.0861-08.2008
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发表时间：
2008-05
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影响因子：
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通讯作者：
C. Takasaki;Rieko Okada;A. Mitani;M. Fukaya;Miwako Yamasaki;Yuri Fujihara;T. Shirakawa;Kohichi Tanaka;Masahiko Watanabe
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文献类型：
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作者：
C. Takasaki;Rieko Okada;A. Mitani;M. Fukaya;Miwako Yamasaki;Yuri Fujihara;T. Shirakawa;Kohichi Tanaka;Masahiko Watanabe
谷氨酸转运蛋白参与神经分化、神经元存活和突触传递。在本研究中，我们检测了 C57BL/6 小鼠新生体感皮层中谷氨酸转运蛋白 1 (GLT1) 的表达，并通过比较 GLT1 敲除小鼠和对照小鼠之间的桶状发育来探究其在体感发育中的作用。在新生儿的最初几天，即桶状发育的关键时期，皮质星形胶质细胞中的 GLT1 表达显着上调，而神经元元件中的 GLT1 表达下调至检测阈值以下。 GLT1敲除的新生儿在身体生长、皮质组织结构、桶形成和关键期终止方面发育正常。然而，当C排胡须在关键时期受损时，GLT1敲除小鼠中受损的C排桶的减少和完整的B/D排桶的相互扩张都比对照同窝小鼠更温和。因此，GLT1 敲除小鼠的图谱可塑性指数（计算为 (B + D)/2C）显着降低。我们还发现 GLT1 敲除小鼠的新生儿体感皮层细胞外谷氨酸水平显着升高。在缺乏谷氨酸-天冬氨酸转运蛋白（GLAST）（一种发育过程中星形胶质细胞特异性谷氨酸转运蛋白）的突变小鼠中，进一步发现损伤诱导的可塑性减弱。因此，谷氨酸转运蛋白通过增强活性桶的扩张和非活性桶的收缩来调节关键期可塑性。由于 GLT1 敲除小鼠中谷氨酸受体和 GLAST 的皮质含量没有改变，因此这种作用似乎至少部分是通过保持环境谷氨酸水平较低来介导的。考虑到谷氨酸受体在胡须相关丘脑皮质突触模式形成中的重要作用，谷氨酸转运蛋白因此促进其活动依赖性重塑。
Glutamate transporters are involved in neural differentiation, neuronal survival, and synaptic transmission. In the present study, we examined glutamate transporter 1 (GLT1) expression in the neonatal somatosensory cortex of C57BL/6 mice, and pursued its role in somatosensory development by comparing barrel development between GLT1 knock-out and control mice. During the first few neonatal days, a critical period for barrels, GLT1 expression is strikingly upregulated in cortical astrocytes, whereas it was downregulated in neuronal elements to below the detection threshold. GLT1 knock-out neonates developed normally in terms of body growth, cortical histoarchitecture, barrel formation, and critical period termination. However, when row C whiskers were lesioned during the critical period, reduction of lesioned row C barrels and reciprocal expansion of intact row B/D barrels were both milder in GLT1 knock-out mice than in control littermates. Accordingly, the map plasticity index, calculated as (B + D)/2C, was significantly lowered in GLT1 knock-out mice. We also found that extracellular glutamate levels in the neonatal somatosensory cortex were significantly elevated in GLT1 knock-out mice. Diminished lesion-induced plasticity was further found in mutant mice lacking glutamate–aspartate transporter (GLAST), an astrocyte-specific glutamate transporter throughout development. Therefore, glutamate transporters regulate critical period plasticity by enhancing expansion of active barrels and shrinkage of inactive barrels. Because cortical contents of glutamate receptors and GLAST were unaltered in GLT1 knock-out mice, this action appears to be mediated, at least partly, by keeping the ambient glutamate level low. Considering an essential role of glutamate receptors in the formation of whisker-related thalamocortical synapse patterning, glutamate transporters thus facilitate their activity-dependent remodeling.