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Puncta of Neuronal Nitric Oxide Synthase (nNOS) Mediate NMDA Receptor Signalling in the Auditory Midbrain

Lookup NU author(s): Dr Bas Olthof, Dr Sasha Gartside, Professor Adrian Rees

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Society for Neuroscience, 2019.

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Abstract

Nitric oxide (NO), is a neurotransmitter synthesised in the brain by neuronal nitric oxide synthase 2 (nNOS). Using immunohistochemistry and confocal imaging in the inferior colliculus (IC, auditory 3 midbrain) of the guinea pig (Cavia porcellus, male and female), we show that nNOS occurs in two 4 distinct cellular distributions. We confirm that in the cortices of the IC, a subset of neurons show 5 cytoplasmic labelling for nNOS, while in the central nucleus (ICC) such neurons are not present. 6 However, we demonstrate that all neurons in the ICC do in fact express nNOS in the form of discrete 7 puncta found at the cell membrane. Our multi-labelling studies reveal that nNOS puncta form multi-8 protein complexes with NMDA receptors, soluble guanylyl cyclase (sGC), and PSD95. These 9 complexes are found apposed to glutamatergic terminals indicative of synaptic function. 10 Interestingly, these glutamatergic terminals express both vesicular glutamate transporters 1 and 2 11 denoting a specific source of brainstem inputs. With in vivo electrophysiological recordings of 12 multiunit activity in the ICC, we found that local application of NMDA enhances sound-driven activity 13 in a concentration-dependent and reversible fashion. This response is abolished by blockade of 14 nNOS or sGC indicating that the NMDA effect is mediated solely via the NO and cGMP signalling 15 pathway. This discovery of a ubiquitous, but highly localised expression, of nNOS throughout the ICC 16 and demonstration of the dramatic influence of the NMDA activated NO pathway on sound-driven 17 neuronal activity, imply a key role for NO signalling in auditory processing.


Publication metadata

Author(s): Othof BMJ, Gartside SE, Rees A

Publication type: Article

Publication status: Published

Journal: Journal of Neuroscience

Year: 2019

Volume: 39

Issue: 5

Pages: 876-887

Print publication date: 30/01/2019

Online publication date: 07/12/2018

Acceptance date: 26/11/2018

Date deposited: 05/12/2018

ISSN (print): 0270-6474

ISSN (electronic): 1529-2401

Publisher: Society for Neuroscience

URL: https://doi.org/10.1523/JNEUROSCI.1918-18.2018

DOI: 10.1523/JNEUROSCI.1918-18.2018


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