AMPA receptor inhibition by synaptically released zinc
AMPA receptor inhibition by synaptically released zinc
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DOI：
10.1073/pnas.1512296112
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发表时间：
2015-12-22
影响因子：
11.1
通讯作者：
Tzounopoulos, Thanos
中科院分区：
文献类型：
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作者：
Kalappa, Bopanna I.;Anderson, Charles T.;Tzounopoulos, Thanos
哺乳动物中枢神经系统中大量的快速兴奋性神经传递是由 AMPA 亚型谷氨酸受体 (AMPAR) 介导的。因此，AMPAR 介导的突触传递几乎涉及大脑发育、功能和可塑性的所有方面。尽管 AMPAR 在神经生物学中发挥着核心作用，但内源性调节剂对突触 AMPA 反应的微调仍然知之甚少。在这里，我们提供的证据表明，由单个突触前动作电位释放的内源性锌会抑制耳蜗背核（DCN）和海马的突触 AMPA 电流。暴露在大声的声音中会降低 DCN 中突触前的锌水平，并消除锌的抑制作用，这表明锌与经验依赖性 AMPAR 突触可塑性有关。我们的研究结果表明，锌是 AMPAR 的一种活性依赖性内源性调节剂，可调节谷氨酸能突触的快速兴奋性神经传递和可塑性。
The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.