Bidirectional modulation of GABA release by presynaptic glutamate receptor 5 kainate receptors in the basolateral amygdala
Bidirectional modulation of GABA release by presynaptic glutamate receptor 5 kainate receptors in the basolateral amygdala
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DOI：
10.1523/jneurosci.23-02-00442.2003
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发表时间：
2003-01-15
影响因子：
5.3
通讯作者：
Li, H
中科院分区：
文献类型：
--
作者：
Braga, MFM;Aroniadou-Anderjaska, V;Li, H
红藻氨酸受体的激活调节GABA能突触传递，但其机制目前仍存在激烈的争论。在基底外侧杏仁核（BLA）中，红藻氨酸受体的谷氨酸受体5（GluR 5）亚基大量表达，GluR 5拮抗剂阻断了一种新形式的突触可塑性;但对含有GluR 5的红藻氨酸受体在杏仁核生理学中的作用知之甚少。在这里，我们表明，GluR 5激动剂双向调节GABA能中间神经元的锥体细胞的突触传递强度的浓度依赖性的方式。低浓度的（RS）-S-氨基-3-（3-羟基-5-叔丁基异恶唑-4-基）（ATPA）（0.3 μ M）或谷氨酸盐（5 μ M）减少GABA能突触传递失败的数量，并增加微型IPSC（mIPSC）的频率。高浓度的ATPA（10 μ M）或谷氨酸（200 μ M）增加了突触失败的数量，降低了mIPSC的频率。GluR 5激动剂促进或抑制GABA能传递不需要激活电压门控钙通道或突触前GABA（B）受体。还发现，细胞外的内源性谷氨酸张力性地降低GABA能传递的失败率。这些结果表明，在BLA的GABA能神经元的终端进行两种亚型的GluR 5-含有红藻氨酸受体，具有不同的激动剂亲和力和激活相反的作用机制。在正常和病理条件下，BLA中谷氨酸盐对GABA释放的GluR 5介导的双向调节可能在该结构中突触可塑性和神经元兴奋性的调节中发挥重要作用。
The activation of kainate receptors modulates GABAergic synaptic transmission, but the mechanisms are currently a matter of intense debate. In the basolateral amygdala (BLA), the glutamate receptor 5 (GluR5) subunit of kainate receptors is heavily expressed, and GluR5 antagonists block a novel form of synaptic plasticity; yet little is known about the role of GluR5-containing kainate receptors in the physiology of the amygdala. Here we show that GluR5 agonists bidirectionally modulate the strength of synaptic transmission from GABAergic interneurons to pyramidal cells in a concentration-dependent manner. Low concentrations of (RS)-S-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) (ATPA) (0.3 muM) or glutamate (5 muM) reduced the number of failures of GABAergic synaptic transmission and enhanced the frequency of miniature IPSCs (mIPSCs). High concentrations of ATPA (10 muM) or glutamate (200 muM) increased the number of synaptic failures and reduced the frequency of mIPSCs. The facilitation or suppression of GABAergic transmission by the GluR5 agonists did not require activation of voltage-gated calcium channels or presynaptic GABA(B) receptors. It was also found that extracellular, endogenous glutamate tonically reduces the rate of failures of GABAergic transmission. These results suggest that the terminals of GABAergic neurons in the BLA carry two subtypes of GluR5-containing kainate receptors, which have different agonist affinities and activate opposing mechanisms of action. The GluR5-mediated, bidirectional modulation of GABA release by glutamate in the BLA may play an important role in the regulation of synaptic plasticity and neuronal excitability in this structure, under normal and pathological conditions.