Astrocytic glutamate uptake is slow and does not limit neuronal NMDA receptor activation in the neonatal neocortex.
Astrocytic glutamate uptake is slow and does not limit neuronal NMDA receptor activation in the neonatal neocortex.
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作者：
Hanson E;Armbruster M;Cantu D;Andresen L;Taylor A;Danbolt NC;Dulla CG
星形胶质细胞摄取谷氨酸控制细胞外间隙谷氨酸的时间进程，并影响神经传递、突触发生和回路发育。星形胶质细胞的谷氨酸摄取已被证明在海马体中经历了出生后的成熟，但在其他大脑区域基本上没有被研究过。值得注意的是，谷氨酸摄取从未在发育中的新皮质中被检测到。在这些研究中，我们研究了发育中的新皮质中星形细胞谷氨酸转运的发展、固有的膜特性以及神经元NMDA受体激活的控制。利用星形胶质细胞和神经元电生理学、免疫荧光和Western印迹分析，我们发现：1)相对于新生海马区，新生新皮质对谷氨酸的摄取缓慢；2)新生新皮质星形胶质细胞的固有膜特性显著成熟；3)谷氨酸摄取缓慢伴随着GLT-1和GLAST的低表达；4)新生儿新皮质谷氨酸摄取对GLT-1的依赖程度低于新生海马区；5)我们报道的新生儿新皮质谷氨酸摄取缓慢对应于星形细胞对神经元NMDA受体激活的最小控制。综上所述，我们的结果清楚地显示了发育中的新皮质和海马区星形胶质细胞成熟之间的根本差异，以及星形胶质细胞如何控制谷氨酸信号的相应变化。
Glutamate uptake by astrocytes controls the time course of glutamate in the extracellular space and affects neurotransmission, synaptogenesis, and circuit development. Astrocytic glutamate uptake has been shown to undergo post-natal maturation in the hippocampus, but has been largely unexplored in other brain regions. Notably, glutamate uptake has never been examined in the developing neocortex. In these studies, we investigated the development of astrocytic glutamate transport, intrinsic membrane properties, and control of neuronal NMDA receptor activation in the developing neocortex. Using astrocytic and neuronal electrophysiology, immunofluorescence, and Western blot analysis we show that: 1) glutamate uptake in the neonatal neocortex is slow relative to neonatal hippocampus; 2) astrocytes in the neonatal neocortex undergo a significant maturation of intrinsic membrane properties; 3) slow glutamate uptake is accompanied by lower expression of both GLT-1 and GLAST; 4) glutamate uptake is less dependent on GLT-1 in neonatal neocortex than in neonatal hippocampus, and 5) the slow glutamate uptake we report in the neonatal neocortex corresponds to minimal astrocytic control of neuronal NMDA receptor activation. Taken together, our results clearly show fundamental differences between astrocytic maturation in the developing neocortex and hippocampus, and corresponding changes in how astrocytes control glutamate signaling.