Nitric oxide regulates the firing rate of neuronal subtypes in the guinea pig ventral cochlear nucleus

Hockley, Adam; Berger, Joel I.; Smith, Paul A.; Palmer, Alan R.; Wallace, Mark N.

Abstract

The gaseous free radical, nitric oxide (NO) acts as a ubiquitous neuromodulator, contributing to synaptic plasticity in a complex way that can involve either long term potentiation or depression. It is produced by neuronal nitric oxide synthase (nNOS) which is presynaptically expressed and also located postsynaptically in the membrane and cytoplasm of a sub-population of each major neuronal type in the ventral cochlear nucleus (VCN). We have used iontophoresis in vivo to study the effect of the NOS inhibitor L-NAME (L-NG-Nitroarginine methyl ester) and the NO donors SIN-1 (3-Morpholinosydnonimine hydrochloride) and SNOG (S-Nitrosoglutathione) on VCN units under urethane anaesthesia. Collectively, both donors produced increases and decreases in driven and spontaneous firing rates of some neurons. Inhibition of endogenous NO production with L-NAME evoked a consistent increase in driven firing rates in 18% of units without much effect on spontaneous rate. This reduction of gain produced by endogenous NO was mirrored when studying the effect of L-NAME on NMDA (N-Methyl-D-aspartic acid)-evoked excitation, with 30% of units showing enhanced NMDA-evoked excitation during L-NAME application (reduced NO levels). Approximately 25% of neurons contain nNOS and the NO produced can modulate the firing rate of the main principal cells: medium stellates (choppers), large stellates (onset responses) and bushy cells (primary like responses). The main endogenous role of NO seems to be to partly suppress driven firing rates associated with NMDA channel activity but there is scope for it to increase neural gain if there were a pathological increase in its production following hearing loss.

Citation

Hockley, A., Berger, J. I., Smith, P. A., Palmer, A. R., & Wallace, M. N. (2020). Nitric oxide regulates the firing rate of neuronal subtypes in the guinea pig ventral cochlear nucleus. European Journal of Neuroscience, 51(4), 963-983. https://doi.org/10.1111/ejn.14572

• Journal Article Type: Article
• Acceptance Date: Aug 29, 2019
• Online Publication Date: Oct 10, 2019
• Publication Date: 2020-02
• Deposit Date: Sep 3, 2019
• Publicly Available Date: Oct 11, 2020
• Journal: European Journal of Neuroscience
• Print ISSN: 0953-816X
• Electronic ISSN: 1460-9568
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 51
• Issue: 4
• Pages: 963-983
• DOI: https://doi.org/10.1111/ejn.14572
• Keywords: Cochlear nucleus, Nitric oxide synthase, Central gain, Auditory system
• Public URL: https://nottingham-repository.worktribe.com/output/2553068
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.14572
• Contract Date: Sep 3, 2019