Cattani Adriano Augusto, Bonfardin Valérie Delphine, Represa Alfonso, Ben-Ari Yehezkel, Aniksztejn Laurent
Institut de Neurobiologie de la Méditerranée (INMED), Institut National de la Santé et de la Recherche Médicale U29 (INSERMU29), Université de la Méditerranée, Marseille, France.
J Neurophysiol. 2007 Oct;98(4):2324-36. doi: 10.1152/jn.00378.2007. Epub 2007 Jul 18.
Cell-surface glutamate transporters are essential for the proper function of early cortical networks because their dysfunction induces seizures in the newborn rat in vivo. We have now analyzed the consequences of their inhibition by DL-TBOA on the activity of the developing CA1 rat hippocampal network in vitro. DL-TBOA generated a pattern of recurrent depolarization with an onset and decay of several seconds' duration in interneurons and pyramidal cells. These slow network oscillations (SNOs) were mostly mediated by gamma-aminobutyric acid (GABA) in pyramidal cells and by GABA and N-methyl-D-aspartate (NMDA) receptors in interneurons. However, in both cell types SNOs were blocked by NMDA receptor antagonists, suggesting that their generation requires a glutamatergic drive. Moreover, in interneurons, SNOs were still generated after the blockade of NMDA-mediated synaptic currents with MK-801, suggesting that SNOs are expressed by the activation of extrasynaptic NMDA receptors. Long-lasting bath application of glutamate or NMDA failed to induce SNOs, indicating that they are generated by periodic but not sustained activation of NMDA receptors. In addition, SNOs were observed in interneurons recorded in slices with or without the strata pyramidale and oriens, suggesting that the glutamatergic drive may originate from the radiatum and pyramidale strata. We propose that in the absence of an efficient transport of glutamate, the transmitter diffuses in the extracellular space to activate extrasynaptic NMDA receptors preferentially present on interneurons that in turn activate other interneurons and pyramidal cells. This periodic neuronal coactivation may contribute to the generation of seizures when glutamate transport dysfunction is present.
细胞表面谷氨酸转运体对于早期皮质网络的正常功能至关重要，因为其功能障碍会在新生大鼠体内诱发癫痫发作。我们现在分析了DL-TBOA对体外培养的发育中的大鼠CA1海马网络活动的抑制作用。DL-TBOA在中间神经元和锥体细胞中产生了一种持续数秒的反复去极化模式。这些缓慢的网络振荡（SNOs）在锥体细胞中主要由γ-氨基丁酸（GABA）介导，在中间神经元中由GABA和N-甲基-D-天冬氨酸（NMDA）受体介导。然而，在这两种细胞类型中，SNOs都被NMDA受体拮抗剂阻断，这表明它们的产生需要谷氨酸能驱动。此外，在中间神经元中，用MK-801阻断NMDA介导的突触电流后仍能产生SNOs，这表明SNOs是由突触外NMDA受体的激活所表达的。长时间浴用谷氨酸或NMDA未能诱导出SNOs，表明它们是由NMDA受体的周期性而非持续性激活所产生的。此外，在有或没有锥体层和海马下托层的切片中记录的中间神经元中都观察到了SNOs，这表明谷氨酸能驱动可能起源于辐射层和锥体层。我们提出，在缺乏有效的谷氨酸转运时，递质在细胞外空间扩散，优先激活中间神经元上存在的突触外NMDA受体，进而激活其他中间神经元和锥体细胞。当存在谷氨酸转运功能障碍时，这种周期性的神经元共同激活可能有助于癫痫发作的产生。
