Park Hyungju, Han Kyung-Seok, Seo Jinsoo, Lee Jaekwang, Dravid Shashank M, Woo Junsung, Chun Heejung, Cho Sukhee, Bae Jin Young, An Heeyoung, Koh Woohyun, Yoon Bo-Eun, Berlinguer-Palmini Rolando, Mannaioni Guido, Traynelis Stephen F, Bae Yong Chul, Choi Se-Young, Lee C Justin
Mol Brain. 2015 Feb 3;8:7. doi: 10.1186/s13041-015-0097-y.
Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca(2+)-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood.
We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity.
Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.
星形胶质细胞中G蛋白偶联受体（GPCR）的激活通过Bestrophin 1（Best1）通道导致钙离子依赖性谷氨酸释放。星形胶质细胞中受体介导的谷氨酸释放是否能调节突触可塑性仍有待充分了解。
我们在此表明，Best1介导的星形胶质细胞谷氨酸激活突触N-甲基-D-天冬氨酸受体（NMDAR）并调节NMDAR依赖性突触可塑性。我们的数据表明，海马CA1区星形胶质细胞中蛋白酶激活受体1（PAR1）的激活提高了Schaffer侧支-CA1（SC-CA1）突触处的谷氨酸浓度，导致含GluN2A的NMDAR激活以及NMDAR依赖性突触反应增强。此外，当星形胶质细胞谷氨酸释放伴随LTP诱导时，诱导NMDAR依赖性长时程增强（LTP）的阈值降低，这表明星形胶质细胞谷氨酸在调节突触可塑性方面具有重要意义。
我们的结果为通道介导的星形胶质细胞谷氨酸在调节神经回路功能中的生理重要性提供了直接证据。
