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

Paul, E. J., Kalk, E., Tossell, K., Irvine, E. E., Franks, N. P., Wisden, W., Withers, D. J., Leiper, J. and Ungless, M. A. (2018) nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta. eNeuro, 5(5), ENEURO.0381-18.2018. (doi: 10.1523/ENEURO.0381-18.2018) (PMID:30456293) (PMCID:PMC6240015)

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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.

Item Type:Articles
Additional Information:This work was supported by United Kingdom Medical Research Council (MRC) Grants MC-A654-5QB70 (to M.A.U.), MC-A654-5QB60 (to J.L.), and MC-A654-5QB40 (to D.J.W.) and by Wellcome Trust Grants 107839/Z/15/Z (toN.P.F.) and 107841/Z/15/Z (to W.W.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leiper, Professor James
Authors: Paul, E. J., Kalk, E., Tossell, K., Irvine, E. E., Franks, N. P., Wisden, W., Withers, D. J., Leiper, J., and Ungless, M. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:eNeuro
Publisher:Society for Neuroscience
ISSN:2373-2822
ISSN (Online):2373-2822
Published Online:29 October 2018
Copyright Holders:Copyright © 2018 Paul et al.
First Published:First published in eNeuro 5(5):ENEURO.0381-18.2018
Publisher Policy:Reproduced under a Creative Commons License

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