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nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta

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Title: nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta
Authors: Paul, EJ
Kalk, E
Tossell, K
Irvine, E
Franks, NP
Wisden, W
Withers, DJ
Leiper, JM
Ungless, MA
Item Type: Journal Article
Abstract: GABA neurons in the VTA and SNc play key roles in reward and aversion through their local inhibitory control of dopamine neuron activity and through long-range projections to several target regions including the nucleus accumbens. It is not clear whether some of these GABA neurons are dedicated local interneurons or if they all collateralize and send projections externally as well as making local synaptic connections. Testing between these possibilities has been challenging in the absence of interneuron-specific molecular markers. We hypothesized that one potential candidate might be neuronal nitric oxide synthase (nNOS), a common interneuronal marker in other brain regions. To test this, we used a combination of immunolabelling (including antibodies for nNOS that we validated in tissue from nNOS-deficient mice) and cell type-specific virus-based anterograde tracing in mice. We found that nNOS-expressing neurons, in the parabrachial pigmented (PBP) part of the VTA and the SNc were GABAergic and did not make detectable projections, suggesting they may be interneurons. In contrast, nNOS-expressing neurons in the rostral linear nucleus (RLi) were mostly glutamatergic and projected to a number of regions, including the lateral hypothalamus (LH), the ventral pallidum (VP), and the median raphe (MnR) nucleus. Taken together, these findings indicate that nNOS is expressed by neurochemically- and anatomically-distinct neuronal sub-groups in a sub-region-specific manner in the VTA and SNc.
Issue Date: 29-Oct-2018
Date of Acceptance: 2-Oct-2018
URI: http://hdl.handle.net/10044/1/65205
DOI: https://dx.doi.org/10.1523/ENEURO.0381-18.2018
ISSN: 2373-2822
Publisher: Society for Neuroscience
Journal / Book Title: eNeuro
Volume: 5
Issue: 5
Copyright Statement: © 2018 Paul et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Wellcome Trust
Medical Research Council
Funder's Grant Number: 107839/Z/15/Z
107841/Z/15/Z
107841/Z/15/Z
MC-A654-5QB40
Keywords: GABA
SNc
VTA
glutamate
nNOS
Publication Status: Published
Online Publication Date: 2018-10-29
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine
Faculty of Natural Sciences



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