期刊
NEUROBIOLOGY OF DISEASE
卷 81, 期 -, 页码 14-19出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2015.03.012
关键词
Zinc; Vesicular zinc transporter; Glycinergic neurotransmission; Spontaneous firing; Auditory brainstem; Dorsal cochlear nucleus
资金
- NIH [RO1-DC007905, F32-DC011664, F32-DC013734-01A1, RO1-GM065519]
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. (C) 2015 Elsevier Inc. All rights reserved.
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