1Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland.
2Neuroscience Center Zurich, University of Zurich and ETH Zurich, CH-8057 Zurich, Switzerland.
Commun Biol. 2019 Apr 5;2:127. doi: 10.1038/s42003-019-0367-9. eCollection 2019.
Removal of synaptically-released glutamate by astrocytes is necessary to spatially and temporally limit neuronal activation. Recent evidence suggests that astrocytes may have specialized functions in specific circuits, but the extent and significance of such specialization are unclear. By performing direct patch-clamp recordings and two-photon glutamate imaging, we report that in the somatosensory cortex, glutamate uptake by astrocytes is slower during sustained synaptic stimulation when compared to lower stimulation frequencies. Conversely, glutamate uptake capacity is increased in the frontal cortex during higher frequency synaptic stimulation, thereby limiting extracellular buildup of glutamate and NMDA receptor activation in layer 5 pyramidal neurons. This efficient glutamate clearance relies on Na/K-ATPase function and both GLT-1 and non-GLT-1 transporters. Thus, by enhancing their glutamate uptake capacity, astrocytes in the frontal cortex may prevent excessive neuronal excitation during intense synaptic activity. These results may explain why diseases associated with network hyperexcitability differentially affect individual brain areas.
星形胶质细胞对突触间隙释放的谷氨酸的清除对于神经元的激活具有时空限制作用。最近的证据表明，星形胶质细胞在特定回路中可能具有特定的功能，但这种特化的程度和意义尚不清楚。通过进行直接膜片钳记录和双光子谷氨酸成像，我们报告称，在体感皮层中，与较低的刺激频率相比，持续的突触刺激期间星形胶质细胞对谷氨酸的摄取较慢。相反，在更高频率的突触刺激期间，前额皮层中的谷氨酸摄取能力增加，从而限制了谷氨酸和 NMDA 受体在第 5 层锥体神经元中的细胞外积累。这种有效的谷氨酸清除依赖于 Na/K-ATP 酶的功能以及 GLT-1 和非-GLT-1 转运体。因此，通过增强其谷氨酸摄取能力，前额叶皮层中的星形胶质细胞可能会防止在强烈的突触活动期间过度兴奋神经元。这些结果可以解释为什么与网络过度兴奋相关的疾病会以不同的方式影响各个脑区。
