Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission
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, t...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/104802 https://orcid.org/0000-0002-2693-4982 |
| _version_ | 1811090876423733248 |
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| author | Perez-Rosello, Tamara Anderson, Charles T. Ling, Cindy Lippard, Stephen J. Tzounopoulos, Thanos |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Perez-Rosello, Tamara Anderson, Charles T. Ling, Cindy Lippard, Stephen J. Tzounopoulos, Thanos |
| author_sort | Perez-Rosello, Tamara |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:53:22Z |
| format | Article |
| id | mit-1721.1/104802 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:53:22Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1048022022-09-29T11:16:53Z Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission Perez-Rosello, Tamara Anderson, Charles T. Ling, Cindy Lippard, Stephen J. Tzounopoulos, Thanos Massachusetts Institute of Technology. Department of Chemistry Lippard, Stephen J. 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. National Institutes of Health (U.S.) (RO1-DC007905) National Institutes of Health (U.S.) (F32-DC011664) National Institutes of Health (U.S.) (F32-DC013734-01A1) National Institutes of Health (U.S.) (RO1-GM065519) 2016-10-13T19:21:18Z 2016-10-13T19:21:18Z 2015-03 2015-03 Article http://purl.org/eprint/type/JournalArticle 09699961 1095-953X http://hdl.handle.net/1721.1/104802 Perez-Rosello, Tamara, Charles T. Anderson, Cindy Ling, Stephen J. Lippard, and Thanos Tzounopoulos. “Tonic Zinc Inhibits Spontaneous Firing in Dorsal Cochlear Nucleus Principal Neurons by Enhancing Glycinergic Neurotransmission.” Neurobiology of Disease 81 (September 2015): 14–19. https://orcid.org/0000-0002-2693-4982 en_US http://dx.doi.org/10.1016/j.nbd.2015.03.012 Neurobiology of Disease Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Perez-Rosello, Tamara Anderson, Charles T. Ling, Cindy Lippard, Stephen J. Tzounopoulos, Thanos Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission |
| title | Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission |
| title_full | Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission |
| title_fullStr | Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission |
| title_full_unstemmed | Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission |
| title_short | Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission |
| title_sort | tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission |
| url | http://hdl.handle.net/1721.1/104802 https://orcid.org/0000-0002-2693-4982 |
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