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A role for nitric oxide in serotonin neurons of the midbrain raphe nuclei

Lookup NU author(s): Dr Sasha Gartside, Shika Amegashiti, Dr Bas Olthof

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley-Blackwell Publishing Ltd, 2020.

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Abstract

Neuronal nitric oxide synthase (nNOS) catalyses the production of the neurotransmitter nitric oxide. nNOS is expressed in the dorsal raphe nucleus (DRN), a source of ascending serotonergic projections. In this study we examined the distribution nNOS and the function of nitric oxide in the DRN and adjacent median raphe nucleus (MRN) of the rat. We hypothesised that nNOS is differentially expressed across the raphe nuclei and that nitric oxide influences the firing activity of a subgroup of 5-HT neurons. Immunohistochemistry revealed that, nNOS is present in around 40% of 5-HT neurons, throughout the DRN and MRN, as well as in some non-5-HT neurons immediately adjacent to the DRN and MRN. The nitric oxide receptor, soluble guanylyl cyclase was present in all 5-HT neurons examined in the DRN and MRN. In vitro extracellular electrophysiology revealed that application of the nitric oxide donor, diethylamine NONOate (30- 300 µM) inhibited 60 - 70% of putative 5-HT neurons, excited approximately 10% of putative 5- HT neurons and had no effect on the rest. The inhibitory response to nitric oxide was blocked by [1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ, 30 or 100 µM), indicating mediation by soluble guanylyl cyclase. Juxtacellular labelling revealed that nitric oxide inhibits firing in both putative 5-HT neurons which express nNOS and those which do not express nNOS. Our data are consistent with the notion that nitric oxide acts as both a trans-synaptic and autocrine signaller in 5-HT neurons in the DRN and MRN and that its effects are widespread and primarily inhibitory.


Publication metadata

Author(s): Gartside SE, Yurttaser AE, Burns AL, Jovanovic N, Smith KJ, Amegashiti NS, Olthof BMJ

Publication type: Article

Publication status: Published

Journal: European Journal of Neuroscience

Year: 2020

Volume: 51

Issue: 9

Pages: 1881-1899

Print publication date: 01/05/2020

Online publication date: 02/03/2020

Acceptance date: 29/02/2020

Date deposited: 04/03/2020

ISSN (print): 0953-816X

ISSN (electronic): 1460-9568

Publisher: Wiley-Blackwell Publishing Ltd

URL: https://doi.org/10.1111/ejn.14713

DOI: 10.1111/ejn.14713


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