Glutamate release from astrocytes as a non-synaptic mechanism for neuronal synchronization in the hippocampus
Glutamate release from astrocytes as a non-synaptic mechanism for neuronal synchronization in the hippocampus
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DOI：
10.1016/j.jphysparis.2005.12.008
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发表时间：
2006-03-01
影响因子：
--
通讯作者：
Fellin, T
中科院分区：
文献类型：
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作者：
Carmignoto, G;Fellin, T
解剖学上分布的神经元组的活动同步代表了大脑中信息处理的基本事件。虽然这种现象被认为是神经元回路内动态相互作用的结果，但神经元群体究竟是如何同步的仍然在很大程度上有待澄清。我们认为星形胶质细胞直接参与海马神经元同步的产生。通过在海马切片制备中结合使用实验方法，包括膜片钳记录和共聚焦显微镜钙成像，我们研究了星形胶质细胞释放的谷氨酸在各种刺激（包括 Schaffer 侧支刺激）下对 CAI 锥体神经元的影响，这些刺激触发了这些神经胶质细胞中 Ca2+ 的升高。我们发现，星形细胞谷氨酸通过优先（如果不是排他地）作用于突触外 NMDA 受体，在 CAI 锥体神经元中引起同步、缓慢的内向电流 (SIC) 和 Ca2+ 升高。由于脱敏作用，除非存在环噻嗪，否则 AMPA 受体不会被星形细胞谷氨酸激活。在几乎没有细胞外镁的情况下，星形胶质细胞释放的谷氨酸被发现在配对记录中引起来自两个 CAI 锥体神经元的高度同步的 SIC，并且在 Ca2+ 成像实验中，在由 2-12 个 CAI 神经元组成的域中同步发生 Ca2+ 升高。在细胞外 Mg2+ (1 mM) 存在的情况下，仍然观察到两个神经元中的同步 SIC 以及神经元域中的同步 Ca2+ 升高，但频率有所降低。我们的结果揭示了星形细胞谷氨酸和突触外 NMDA 受体之间的功能联系，有助于神经元同步的整体动态。我们的观察还提出了一系列关于星形胶质细胞到神经元信号传导在海马病理变化（例如兴奋毒性神经元损伤或癫痫样活动的产生）中可能发挥的作用的问题。 (c) 2006 Elsevier Ltd. 保留所有权利。
Synchronization of activity of anatomically distributed groups of neurons represents a fundamental event in the processing of information in the brain. While this phenomenon is believed to result from dynamic interactions within the neuronal circuitry, how exactly populations of neurons become synchronized remains largely to be clarified. We propose that astrocytes are directly involved in the generation of neuronal synchrony in the hippocampus. By using a combination of experimental approaches in hippocampal slice preparations, including patch-clamp recordings and confocal microscopy calcium imaging, we studied the effect on CAI pyramidal neurons of glutamate released from astrocytes upon various stimuli that trigger Ca2+ elevations in these glial cells, including Schaffer collateral stimulation. We found that astrocytic glutamate evokes synchronous, slow inward currents (SICs) and Ca2+ elevations in CAI pyramidal neurons by acting preferentially, if not exclusively, on extrasynaptic NMDA receptors. Due to desensitization, AMPA receptors were not activated by astrocytic glutamate unless cyclothiazide was present. In the virtual absence of extracellular Mg, glutamate released from astrocytes was found to evoke, in paired recordings, highly synchronous SICs from two CAI pyramidal neurons and, in Ca2+ imaging experiments, Ca2+ elevations that occurred synchronously in domains composed of 2-12 CAI neurons. In the presence of extracellular Mg2+ (1 mM), synchronous SICs in two neurons as well as synchronous Ca2+ elevations in neuronal domains were still observed, although with a reduced frequency. Our results reveal a functional link between astrocytic glutamate and extrasynaptic NMDA receptors that contributes to the overall dynamics of neuronal synchrony. Our observations also raise a series of questions on possible roles of this astrocyte-to-neuron signaling in pathological changes in the hippocampus such as excitotoxic neuronal damage or the generation of epileptiform activity. (c) 2006 Elsevier Ltd. All rights reserved.