Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Eur J Neurosci. 2010 Nov;32(10):1668-77. doi: 10.1111/j.1460-9568.2010.07452.x. Epub 2010 Oct 19.
The maintenance of synaptic functions is essential for neuronal information processing in the adult brain. Astrocytes express glutamate transporters that rapidly remove glutamate from the extracellular space and they play a critical role in the precise operation of glutamatergic transmission. However, how the glutamate clearance function of astrocytes is maintained remains elusive. Here, we describe a maintenance mechanism for the glutamate uptake capacity of Bergmann glial cells (BGs) in the cerebellum. When inositol 1,4,5-trisphosphate (IP(3) ) signaling was chronically and selectively inhibited in BGs in vivo, the retention time of glutamate around parallel fiber-Purkinje cell synapses was increased. Under these conditions, a decrease in the level of the glutamate/aspartate transporter (GLAST) in BGs was observed. The same effects were observed after chronic in vivo inhibition of purinergic P2 receptors in the cerebellar cortex. These results suggest that the IP(3) signaling cascade is involved in regulating GLAST levels in BGs to maintain glutamate clearance in the mature cerebellum.
维持突触功能对于成年大脑中的神经元信息处理至关重要。星形胶质细胞表达谷氨酸转运体，可迅速将谷氨酸从细胞外间隙中清除，它们在谷氨酸能传递的精确运作中发挥着关键作用。然而，星形胶质细胞的谷氨酸清除功能是如何维持的仍然难以捉摸。在这里，我们描述了小脑伯格曼胶质细胞（BGs）中谷氨酸摄取能力的维持机制。当在体内慢性且选择性地抑制 BG 中的肌醇 1,4,5-三磷酸（IP（3））信号时，平行纤维-浦肯野细胞突触周围谷氨酸的保留时间增加。在这些条件下，BG 中的谷氨酸/天冬氨酸转运体（GLAST）水平下降。在小脑皮层中慢性体内抑制嘌呤能 P2 受体后也观察到相同的效果。这些结果表明，IP（3）信号级联参与调节 BG 中的 GLAST 水平，以维持成熟小脑的谷氨酸清除。
