Astrocyte activation of presynaptic metabotropic glutamate receptors modulates hippocampal inhibitory synaptic transmission
Astrocyte activation of presynaptic metabotropic glutamate receptors modulates hippocampal inhibitory synaptic transmission
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DOI：
10.1017/s1740925x05000190
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发表时间：
2004-01-01
影响因子：
--
通讯作者：
Nedergaard, Maiken
中科院分区：
文献类型：
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作者：
Liu, Qing-Song;Xu, Qiwu;Nedergaard, Maiken
在中枢神经系统中，星形胶质细胞的细小突起通常包裹树突、轴突和突触，这提供了神经元和星形胶质细胞可能相互作用的界面。我们以前曾报道过，选择性的钙离子在星形胶质细胞的升高，通过光分解笼中的钙离子邻硝基苯基-EGTA（NP-EGTA），导致红藻氨酸受体依赖性增加的频率在相邻的中间神经元在海马切片的自发抑制性突触后电位（sIPSC）。然而，河豚毒素（TTX），它阻止动作电位，减少在中间神经元中的微型IPSC（mIPSC）的频率在Ca 2 + uncaging通过一个未知的突触前机制。在本研究中，我们探讨了突触前抑制的机制。我们发现，星形胶质细胞中的Ca 2+释放伴随着邻近中间神经元中诱发的IPSC（eIPSC）的振幅降低。CPPG（一种II/III组代谢型谷氨酸受体（mGluR）拮抗剂）可阻止eIPSC振幅和mIPSC频率的降低，但AMPA/红藻氨酸和NMDA受体拮抗剂CNQX/CPP不能阻止。应用II组mGluR激动剂DCG IV或III组mGluR激动剂L-AP（4）通过突触前机制降低eIPSC的振幅，并且这两种作用都被CPPG阻断。因此，mGluRs的活化介导Ca 2+解除对mIPSC和eIPSC的作用。我们的研究结果表明，钙依赖性释放谷氨酸从星形胶质细胞可以激活不同类别的谷氨酸受体和差异调节抑制性突触传递海马中间神经元。
In the CNS, fine processes of astrocytes often wrap around dendrites, axons and synapses, which provides an interface where neurons and astrocytes might interact. We have reported previously that selective Ca2+ elevation in astrocytes, by photolysis of caged Ca2+ by o-nitrophenyl-EGTA (NP-EGTA), causes a kainite receptor-dependent increase in the frequency of spontaneous inhibitory post-synaptic potentials (sIPSCs) in neighboring interneurons in hippocampal slices. However, tetrodotoxin (TTX), which blocks action potentials, reduces the frequency of miniature IPSCs (mIPSCs) in interneurons during Ca2+ uncaging by an unknown presynaptic mechanism. In this study we investigate the mechanism underlying the presynaptic inhibition. We show that Ca2+ uncaging in astrocytes is accompanied by a decrease in the amplitude of evoked IPSCs (eIPSCs) in neighboring interneurons. The decreases in eIPSC amplitude and mIPSC frequency are prevented by CPPG, a group II/III metabotropic glutamate receptor (mGluR) antagonist, but not by the AMPA/kainate and NMDA receptor antagonists CNQX/CPP. Application of either the group II mGluR agonist DCG IV or the group III mGluR agonist L-AP(4) decreased the amplitude of eIPSCs by a presynaptic mechanism, and both effects are blocked by CPPG. Thus, activation of mGluRs mediates the effects of Ca2+ uncaging on mIPSCs and eIPSCs. Our results indicate that Ca2+-dependent release of glutamate from astrocytes can activate distinct classes of glutamate receptors and differentially modulate inhibitory synaptic transmission in hippocampal interneurons.