Modulation of glutamatergic transmission by Bergmann glial cells in rat cerebellum in situ
Modulation of glutamatergic transmission by Bergmann glial cells in rat cerebellum in situ
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DOI：
10.1152/jn.00904.2002
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发表时间：
2003-02-01
影响因子：
2.5
通讯作者：
Sontheimer, H
中科院分区：
文献类型：
--
作者：
Bordey, A;Sontheimer, H
我们从小脑脑片的神经元-胶质细胞对获得膜片钳记录，以研究Bergmann胶质细胞摄取谷氨酸（Glu）对形成平行纤维-浦肯野细胞突触的兴奋性突触后电流（EPSC）的贡献。我们发现，电刺激平行纤维不仅激活EPSC浦肯野细胞，但也激活内向电流抗原识别的Bergmann胶质细胞投资浦肯野细胞突触与他们的进程。内向电流部分是由6-氰基-7-硝基喹喔啉-2，3-二酮（CNQX）和2-氨基-5-磷酸戊酸（AP 5）敏感的离子型Glu受体介导的，但大于或等于70%的电流是由D，L-苏型-β-羟基天冬氨酸（THA）敏感的Glu转运蛋白介导的。Glu内向电流被完全可逆地抑制，通过Bergmann神经胶质细胞去极化至正膜电位，允许生物物理抑制Glu摄取至单个神经胶质细胞。通过电压钳制细胞去极化电位抑制Glu转运到Bergmann神经胶质细胞引起浦肯野细胞自发EPSC频率的可逆增加。这种增加也可以通过Glu转运抑制剂THA对Glu转运的药理学抑制来实现，这表明抑制Glu摄取到Bergmann神经胶质细胞中负责突触后EPSC的调制。THA调制的自发EPSC只能在没有TTX的情况下观察到，这主要表明突触前效应。总之，这些数据表明，神经胶质细胞的谷氨酸摄取可以深刻地影响兴奋性传递小脑，最有可能通过调节突触前谷氨酸释放。
We obtained patch-clamp recordings from neuron-glial cell pairs in cerebellar brain slices to examine the contribution of glutamate (Glu) uptake by Bergmann glial cells to shaping excitatory postsynaptic currents (EPSCs) at the parallel fiber to Purkinje cell synapse. We show that electrical stimulation of parallel fibers not only activates EPSCs in Purkinje cells but also activates inward currents in antigenically identified Bergmann glial cells that invest Purkinje cell synapse with their processes. The inward current is partially due to 6-cyano-7-nitroquinoxalene- 2,3-dione (CNQX)- and 2-amino-5-phosphonopentanoic acid (AP5)-sensitive ionotropic Glu receptors, but greater than or equal to70% of the current was mediated by D, L-threo-beta-hydroxyaspartate (THA) sensitive Glu transporters. Glu inward currents were completely and reversibly inhibited by depolarization of Bergmann glial cells to positive membrane potentials allowing biophysical inhibition of Glu uptake into a single glial cell. Inhibition of Glu transport into Bergmann glial cells by voltage-clamping the cell to depolarized potentials caused a reversible increase in spontaneous EPSC frequency in the Purkinje cell. This increase could also be achieved by pharmacological inhibition of Glu transport with the Glu transport inhibitor THA, suggesting that inhibition of Glu uptake into Bergmann glial cells is responsible for the modulation of postsynaptic EPSCs. THA modulation of spontaneous EPSCs could only be observed in the absence of TTX, suggesting primarily a presynaptic effect. Taken together these data suggest that glial Glu uptake can profoundly affect excitatory transmission in the cerebellum, most likely by regulating presynaptic glutamate release.