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

Autor: Gartside SE; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK., Yurttaser AE; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK., Burns AL; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK., Jovanović N; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK., Smith KJ; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK., Amegashiti NS; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK., Olthof BMJ; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2020 May; Vol. 51 (9), pp. 1881-1899. Date of Electronic Publication: 2020 Mar 13.
DOI: 10.1111/ejn.14713
Abstrakt: 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 hypothesized 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.
(© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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