Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons
Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons
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DOI：
10.1046/j.1460-9568.1998.00221.x
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发表时间：
1998-06-01
影响因子：
3.4
通讯作者：
Haydon, PG
中科院分区：
文献类型：
--
作者：
Araque, A;Parpura, V;Haydon, PG
星形胶质细胞仅为神经元提供结构和营养支持的观点已被星形胶质细胞调节神经元钙水平的证明所挑战。然而，星形细胞-神经元信号传导的生理后果尚不清楚。利用大鼠海马星形胶质细胞和神经元的混合培养，我们确定了星形胶质细胞钙水平升高对共培养神经元的功能影响。电或机械刺激星形胶质细胞以增加其钙水平，导致相关神经元中谷氨酸依赖的缓慢内向电流（SIC）。将1,2-二（2-氨基苯氧基）乙烷-N，N，N‘，N’-四乙酸（BAPTA）微量注射到星形胶质细胞中，以防止星形胶质细胞钙水平的刺激依赖性增加，阻断神经元SIG的出现。药理学操作表明，这种星形胶质细胞依赖性SIC是由作用于N-甲基-d -天冬氨酸（NMDA）和非NMDA谷氨酸受体的细胞外谷氨酸介导的。此外，星形胶质细胞的刺激通过激活代谢性谷氨酸受体，降低了动作电位诱发的兴奋性和抑制性突触后电流的大小。星形胶质细胞调节神经元电流和突触传递的证明提出了星形胶质细胞通过控制细胞外谷氨酸水平发挥神经调节作用的可能性。
The idea that astrocytes merely provide structural and trophic support for neurons has been challenged by the demonstration that astrocytes can regulate neuronal calcium levels. However, the physiological consequences of astrocyte-neuron signalling are unknown. Using mixed cultures of rat hippocampal astrocytes and neurons we have determined functional consequences of elevating astrocyte calcium levels on co-cultured neurons. Electrical or mechanical stimulation of astrocytes to increase their calcium level caused a glutamate-dependent slow inward current (SIC) in associated neurons. Microinjection of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) into astrocytes to prevent the stimulus-dependent increase in astrocyte calcium level, blocks the appearance of the neuronal SIG. Pharmacological manipulations indicate that this astrocyte-dependent SIC is mediated by extracellular glutamate acting on N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. Additionally, stimulation of astrocytes reduced the magnitude of action potential-evoked excitatory and inhibitory postsynaptic currents through the activation of metabotropic glutamate receptors. The demonstration that astrocytes modulate neuronal currents and synaptic transmission raises the possibility that astrocytes play a neuromodulatory role by controlling the extracellular level of glutamate.