Astrocytic GABA transporter activity modulates excitatory neurotransmission.
Astrocytic GABA transporter activity modulates excitatory neurotransmission.
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DOI：
10.1038/ncomms13572
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发表时间：
2016-11-25
影响因子：
16.6
通讯作者：
Walker, Matthew C.
中科院分区：
文献类型：
--
作者：
Boddum, Kim;Jensen, Thomas P.;Magloire, Vincent;Kristiansen, Uffe;Rusakov, Dmitri A.;Pavlov, Ivan;Walker, Matthew C.
星形胶质细胞是检测和响应网络活动的理想位置。它们表达亲离子和亲代谢性受体，并能释放神经胶质递质。星形胶质细胞还表达调节细胞外神经递质浓度的转运蛋白。在这里，我们报告了星形细胞GABA转运体GAT-3以前未被认识到的作用。GAT-3活性导致星形胶质细胞Na+浓度升高，进而通过Na+/Ca~(2+)交换导致星形胶质细胞Ca~(2+)浓度升高。这导致星形胶质细胞释放ATP/腺苷，然后通过激活突触前腺苷受体来扩散地抑制神经元谷氨酸的释放。通过这一机制，由中间神经元释放的GABA导致星形胶质细胞GAT-3活性增加，从而导致弥漫性的异突触抑制。这为海马区兴奋性传递的动态平衡调节提供了一种机制。星形胶质细胞监控和调节兴奋性和抑制性突触活动。在这里，作者发现了一种新的神经元-胶质细胞通讯形式，星形胶质细胞通过GABA转运体GAT-3检测GABA的上升；这导致腺苷释放，在突触前作用，抑制神经谷氨酸能信号。
Astrocytes are ideally placed to detect and respond to network activity. They express ionotropic and metabotropic receptors, and can release gliotransmitters. Astrocytes also express transporters that regulate the extracellular concentration of neurotransmitters. Here we report a previously unrecognized role for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in astrocytic Na+ concentrations and a consequent increase in astrocytic Ca2+ through Na+/Ca2+ exchange. This leads to the release of ATP/adenosine by astrocytes, which then diffusely inhibits neuronal glutamate release via activation of presynaptic adenosine receptors. Through this mechanism, increases in astrocytic GAT-3 activity due to GABA released from interneurons contribute to 'diffuse' heterosynaptic depression. This provides a mechanism for homeostatic regulation of excitatory transmission in the hippocampus. Astrocytes monitor and regulate both excitatory and inhibitory synaptic activity. Here, the authors identify a novel form of neuronal-glia communication, by which astrocytes detect rises in GABA via the GABA transporter GAT-3; this results in adenosine release that acts presynaptically to inhibit neural glutamatergic signalling.
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影响因子：
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影响因子：
56.9
作者：
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