Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission.
Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission.
复制标题
补锌通过增强甘氨酸神经传递来抑制耳蜗背核主要神经元的自发放电。
DOI：
10.1016/j.nbd.2015.03.012
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发表时间：
2015
影响因子：
6.1
通讯作者：
Tzounopoulos,Thanos
中科院分区：
文献类型：
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作者：
Perez-Rosello,Tamara;Anderson,CharlesT;Ling,Cindy;Lippard,StephenJ;Tzounopoulos,Thanos
在中枢神经系统的许多突触中，移动的锌被包装到谷氨酸能囊泡中，并在神经传递过程中与谷氨酸共同释放。突触释放后，动员锌调节配体和电压门控通道和受体，作为一种抑制性神经调质。然而，补药的起源和作用，而不是阶段性释放，锌是不太清楚。我们研究了耳蜗背核（DCN）中的补锌，DCN是一个富含锌的听觉脑干核。我们的研究结果表明，应用高亲和力，细胞外锌螯合剂（ZX1）增强DCN主神经元（梭形细胞）的自发放电，与抑制这种神经元的性质由补锌一致。事先应用士的宁（一种甘氨酸受体拮抗剂）可阻止增强效应，这表明ZX1干扰锌介导的自发甘氨酸抑制调节。特别是，ZX1降低的幅度和频率的甘氨酸能微型抑制性突触后电流的梭形细胞，从我们得出的结论，补锌增强甘氨酸能抑制性神经传递。所观察到的锌介导的自发放电抑制存在于缺乏囊泡锌转运蛋白（ZnT3）的小鼠中，表明非囊泡锌抑制自发放电。噪声引起的梭形细胞自发放电的增加对于耳鸣的诱导至关重要。在这种情况下，补锌提供了一个强大的中断自发放电，可以防止病理运行的自发活动在DCN。
In many synapses of the CNS, mobile zinc is packaged into glutamatergic vesicles and co-released with glutamate during neurotransmission. Following synaptic release, the mobilized zinc modulates ligand- and voltage-gated channels and receptors, functioning as an inhibitory neuromodulator. However, the origin and role of tonic, as opposed to phasically released, zinc are less well understood. We investigated tonic zinc in the dorsal cochlear nucleus (DCN), a zinc-rich, auditory brainstem nucleus. Our results show that application of a high-affinity, extracellular zinc chelator (ZX1) enhances spontaneous firing in DCN principal neurons (fusiform cells), consistent with inhibition of this neuronal property by tonic zinc. The enhancing effect was prevented by prior application of strychnine, a glycine receptor antagonist, suggesting that ZX1 interferes with zinc-mediated modulation of spontaneous glycinergic inhibition. In particular, ZX1 decreased the amplitude and the frequency of glycinergic miniature inhibitory postsynaptic currents in fusiform cells, from which we conclude that tonic zinc enhances glycinergic inhibitory neurotransmission. The observed zinc-mediated inhibition in spontaneous firing is present in mice lacking the vesicular zinc transporter (ZnT3), indicating that non-vesicular zinc inhibits spontaneous firing. Noise-induced increase in the spontaneous firing of fusiform cells is crucial for the induction of tinnitus. In this context, tonic zinc provides a powerful break of spontaneous firing that may protect against pathological run-up of spontaneous activity in the DCN.