Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission

Neurobiology of Disease
Tamara Perez-RoselloThanos Tzounopoulos

Abstract

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 th...Continue Reading

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Citations

May 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Charles T AndersonThanos Tzounopoulos
Nov 7, 2015·Neurobiology of Disease·Elias Aizenman, Pier G Mastroberardino
Oct 8, 2016·Frontiers in Molecular Neuroscience·Yan ZhangJoseph W Lynch
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May 8, 2019·Journal of Neurochemistry·Alexander AugustStefan Kins
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Feb 14, 2017·Israel Journal of Chemistry·Jacob M GoldbergStephen J Lippard
May 11, 2017·Essays in Biochemistry·Chelsea A Barr, Shawn C Burdette
Dec 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Bopanna I KalappaThanos Tzounopoulos
Jan 19, 2021·Neuroscience·Rebecca F KrallElias Aizenman

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