Bellamy Tomas C, Ogden David
National Institute for Medical Research, London, United Kingdom.
Glia. 2005 Dec;52(4):325-35. doi: 10.1002/glia.20248.
Bergmann glial cells (BGC) enclose the synapses of Purkinje neurons (PN) and interneurons in the molecular layer of the cerebellar cortex. During synaptic transmission, glutamate evokes inward currents in the glia by activation of Ca2+-permeable aminohydroxymethylisoxazole propionic acid receptors (AMPAR) and electrogenic transporters. We describe the plasticity of BGC currents during paired-pulse and repetitive stimulation of parallel fibers in cerebellar slices. Paired-pulse facilitation (PPF) of BGC AMPAR currents was 4-fold, twice that of PN PPF. Experiments with a low-affinity AMPAR antagonist showed an increase in extrasynaptic glutamate concentration during the second pulse of the pair. PPF of glial transporter currents was 1.8-fold, similar to synaptic PPF. Tetanic stimulation revealed that facilitation of BGC AMPAR currents is not sustained during high-frequency stimulation, and substantial depression is observed after a few pulses. Consequently, Ca2+ influx through glial AMPARs would initially be facilitated but subsequently depressed, generating a transient Ca2+ influx in response to a sustained tetanus. This pattern of plasticity may be important in enabling Bergmann glial cell processes to detect and support synapses with high-frequency input. Finally, a new current was observed in BGC during repetitive stimulation. It was blocked by NBQX and intracellular GDP-beta-S, increased by glutamate uptake inhibition, had PPF similar to synaptic PPF, and was unaffected by an inhibitor of fast glial AMPAR currents. The evidence suggests that activation of neuronal AMPARs causes the release of a paracrine messenger to activate a G-protein coupled receptor in the BGC.
伯格曼胶质细胞（BGC）包围着小脑皮质分子层中浦肯野神经元（PN）和中间神经元的突触。在突触传递过程中，谷氨酸通过激活钙离子通透的氨基羟甲基异恶唑丙酸受体（AMPAR）和电转运体在胶质细胞中引发内向电流。我们描述了在小脑切片中对平行纤维进行双脉冲和重复刺激时BGC电流的可塑性。BGC的AMPAR电流双脉冲易化（PPF）为4倍，是PN的PPF的两倍。使用低亲和力AMPAR拮抗剂的实验表明，在双脉冲的第二个脉冲期间，突触外谷氨酸浓度增加。胶质细胞转运体电流的PPF为1.8倍，与突触PPF相似。强直刺激表明，在高频刺激期间，BGC的AMPAR电流的易化不能持续，并且在几个脉冲后会出现明显的抑制。因此，通过胶质细胞AMPAR的钙离子内流最初会得到促进，但随后会受到抑制，从而在持续强直刺激时产生短暂的钙离子内流。这种可塑性模式对于使伯格曼胶质细胞过程能够检测和支持高频输入的突触可能很重要。最后，在重复刺激期间在BGC中观察到一种新电流。它被NBQX和细胞内GDP-β-S阻断，通过抑制谷氨酸摄取而增加，具有与突触PPF相似的PPF，并且不受快速胶质细胞AMPAR电流抑制剂的影响。证据表明，神经元AMPAR的激活会导致旁分泌信使的释放，从而激活BGC中的G蛋白偶联受体。
