Direct modulation of synaptic vesicle priming by GABAB receptor activation at a glutamatergic synapse
Direct modulation of synaptic vesicle priming by GABAB receptor activation at a glutamatergic synapse
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DOI：
10.1038/nature01859
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发表时间：
2003-08-14
期刊：
影响因子：
64.8
通讯作者：
Neher, E
中科院分区：
文献类型：
--
作者：
Sakaba, T;Neher, E
已知涉及G蛋白（1，2）和钙（3）的第二信使级联调节神经递质释放（4，5）。这种级联反应的一个显著影响是突触前钙内流的下调（6，7），这显著减少了诱发的神经递质释放（5，7，8）。在这里，我们表明，G-蛋白介导的信号，如通过GABA（γ-氨基丁酸）亚型B（GABA（B））受体，延缓在持续活动和短期抑郁后的突触囊泡的招聘。这种阻滞通过降低环AMP而发生，环AMP阻断了钙浓度增加对囊泡募集的刺激作用。在该信号通路中，cAMP（通过cAMP依赖性鸟嘌呤核苷酸交换因子起作用）和钙/钙调蛋白合作以增强囊泡引发。两种形式的突触可塑性，突触前抑制和钙依赖性恢复突触抑制的差异调制，预计将有有趣的后果神经网络的动态行为。
Second messenger cascades involving G proteins(1,2) and calcium(3) are known to modulate neurotransmitter release(4,5). A prominent effect of such a cascade is the downmodulation of presynaptic calcium influx(6,7), which markedly reduces evoked neurotransmitter release(5,7,8). Here we show that G-protein-mediated signalling, such as through GABA (gamma-amino butyric acid) subtype B (GABA(B)) receptors, retards the recruitment of synaptic vesicles during sustained activity and after short-term depression. This retardation occurs through a lowering of cyclic AMP, which blocks the stimulatory effect of increased calcium concentration on vesicle recruitment. In this signalling pathway, cAMP (functioning through the cAMP-dependent guanine nucleotide exchange factor) and calcium/calmodulin cooperate to enhance vesicle priming. The differential modulation of the two forms of synaptic plasticity, presynaptic inhibition and calcium-dependent recovery from synaptic depression, is expected to have interesting consequences for the dynamic behaviour of neural networks.