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Lookup NU author(s): Dr Bas OlthofORCiD,
Dr Sasha Gartside,
Professor Adrian ReesORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Society for Neuroscience, 2019.
For re-use rights please refer to the publisher's terms and conditions.
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.
Author(s): Othof BMJ, Gartside SE, Rees A
Publication type: Article
Publication status: Published
Journal: Journal of Neuroscience
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
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