Nitric oxide increases gain in the ventral cochlear nucleus of guinea pigs with tinnitus

Hockley, Adam; Berger, Joel I; Palmer, Alan R; Wallace, Mark N

Abstract

Previous work has led to the hypothesis that, during the production of noise?induced tinnitus, higher levels of nitric oxide (NO), in the ventral cochlear nucleus (VCN), increase the gain applied to a reduced input from the cochlea. To test this hypothesis, we noise?exposed 26 guinea pigs, identified evidence of tinnitus in 12 of them and then compared the effects of an iontophoretically applied NO donor or production inhibitor on VCN single unit activity. We confirmed that the mean driven firing rate for the tinnitus and control groups were the same while it had fallen in the non?tinnitus group. By contrast, the mean spontaneous rate had increased for the tinnitus group relative to control while it remained the same for the non?tinnitus group. A greater proportion of units responded to exogenously applied NO in the tinnitus (56%) and non?tinnitus groups (71%) than a control population (24%). In the tinnitus group, endogenous NO facilitated the driven firing rate in 37% (7/19) of neurons and appeared to bring the mean driven rate back up to control levels by a mechanism involving N?Methyl?D?aspartic acid (NMDA) receptors. By contrast, in the non?tinnitus group, endogenous NO only facilitated the driven firing rate in 5% (1/22) of neurons and there was no facilitation of driven rate in the control group. The effects of endogenous NO on spontaneous activity were unclear. These results suggest that NO is involved in increasing the gain applied to driven activity but other factors are also involved in the increase in spontaneous activity.

Citation

Hockley, A., Berger, J. I., Palmer, A. R., & Wallace, M. N. (2020). Nitric oxide increases gain in the ventral cochlear nucleus of guinea pigs with tinnitus. European Journal of Neuroscience, 52(9), 4057-4080. https://doi.org/10.1111/ejn.14913

• Journal Article Type: Article
• Acceptance Date: Jul 11, 2020
• Online Publication Date: Aug 1, 2020
• Publication Date: 2020-11
• Deposit Date: Jul 13, 2020
• Publicly Available Date: Aug 2, 2021
• Journal: European Journal of Neuroscience
• Print ISSN: 0953-816X
• Electronic ISSN: 1460-9568
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 52
• Issue: 9
• Pages: 4057-4080
• DOI: https://doi.org/10.1111/ejn.14913
• Keywords: synaptic plasticity; noise exposure; central auditory system; spontaneous activity
• Public URL: https://nottingham-repository.worktribe.com/output/4765118
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.14913