Piet Richard, Vargová Lydia, Syková Eva, Poulain Dominique A, Oliet Stéphane H R
Institut National de la Santé et de la Recherche Médicale Unité 378, Institut François Magendie, Université Victor Segalen Bordeaux 2, 33077 Bordeaux, France.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2151-5. doi: 10.1073/pnas.0308408100. Epub 2004 Feb 6.
Interactions between separate synaptic inputs converging on the same target appear to contribute to the fine-tuning of information processing in the central nervous system. Intersynaptic crosstalk is made possible by transmitter spillover from the synaptic cleft and its diffusion over a distance to neighboring synapses. This is the case for glutamate, which inhibits gamma-aminobutyric acid (GABA)ergic transmission in several brain regions through the activation of presynaptic receptors. Such heterosynaptic modulation depends on factors that influence diffusion in the extracellular space (ECS). Because glial cells represent a physical barrier to diffusion and, in addition, are essential for glutamate uptake, we investigated the physiological contribution of the astrocytic environment of neurons to glutamate-mediated intersynaptic communication in the brain. Here we show that the reduced astrocytic coverage of magnocellular neurons occurring in the supraoptic nucleus of lactating rats facilitates diffusion in the ECS, as revealed by tortuosity and volume fraction measurements. Under these conditions, glutamate spillover, monitored through metabotropic glutamate receptor-mediated depression of GABAergic transmission, is greatly enhanced. Conversely, impeding diffusion with dextran largely prevents crosstalk between glutamatergic and GABAergic afferent inputs. Astrocytes, therefore, by hindering diffusion in the ECS, regulate intersynaptic communication between neighboring synapses and, probably, overall volume transmission in the brain.
汇聚于同一靶点的不同突触输入之间的相互作用，似乎有助于中枢神经系统中信息处理的精细调节。突触间的串扰可通过递质从突触间隙溢出并扩散至邻近突触来实现。谷氨酸就是这种情况，它通过激活突触前受体，在多个脑区抑制γ-氨基丁酸（GABA）能传递。这种异突触调制取决于影响细胞外空间（ECS）中扩散的因素。由于神经胶质细胞是扩散的物理屏障，此外，对谷氨酸摄取至关重要，我们研究了神经元的星形胶质细胞环境对大脑中谷氨酸介导的突触间通讯的生理贡献。在此我们表明，通过曲折度和体积分数测量发现，泌乳大鼠视上核中发生的大细胞神经元星形胶质细胞覆盖减少，促进了ECS中的扩散。在这些条件下，通过代谢型谷氨酸受体介导的GABA能传递抑制来监测的谷氨酸溢出大大增强。相反，用葡聚糖阻碍扩散在很大程度上阻止了谷氨酸能和GABA能传入输入之间的串扰。因此，星形胶质细胞通过阻碍ECS中的扩散，调节邻近突触之间的突触间通讯，可能还调节大脑中的整体容积传递。
