Imperial College London

ProfessorDominicWithers

Faculty of MedicineInstitute of Clinical Sciences

Clinical Chair in Diabetes & Endocrinology
 
 
 
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Contact

 

d.withers

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Paul:2018:10.1523/ENEURO.0381-18.2018,
author = {Paul, EJ and Kalk, E and Tossell, K and Irvine, E and Franks, NP and Wisden, W and Withers, DJ and Leiper, JM and Ungless, MA},
doi = {10.1523/ENEURO.0381-18.2018},
journal = {eNeuro},
title = {nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta},
url = {http://dx.doi.org/10.1523/ENEURO.0381-18.2018},
volume = {5},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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.
AU - Paul,EJ
AU - Kalk,E
AU - Tossell,K
AU - Irvine,E
AU - Franks,NP
AU - Wisden,W
AU - Withers,DJ
AU - Leiper,JM
AU - Ungless,MA
DO - 10.1523/ENEURO.0381-18.2018
PY - 2018///
SN - 2373-2822
TI - nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta
T2 - eNeuro
UR - http://dx.doi.org/10.1523/ENEURO.0381-18.2018
UR - http://hdl.handle.net/10044/1/65205
VL - 5
ER -