Transcriptional profiling aligned with in situ expression image analysis reveals mosaically expressed molecular markers for GABA neuron sub-groups in the ventral tegmental area.


Journal

The European journal of neuroscience
ISSN: 1460-9568
Titre abrégé: Eur J Neurosci
Pays: France
ID NLM: 8918110

Informations de publication

Date de publication:
12 2019
Historique:
received: 26 04 2019
revised: 12 07 2019
accepted: 19 07 2019
pubmed: 3 8 2019
medline: 4 9 2020
entrez: 3 8 2019
Statut: ppublish

Résumé

γ-Aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA) provide local inhibitory control of dopamine neuron activity and send long-range projections to several target regions including the nucleus accumbens. They play diverse roles in reward and aversion, suggesting that they be comprised of several functionally distinct sub-groups, but our understanding of this diversity has been limited by a lack of molecular markers that might provide genetic entry points for cell type-specific investigations. To address this, we conducted transcriptional profiling of GABA neurons and dopamine neurons using immunoprecipitation of tagged polyribosomes (RiboTag) and RNAseq. First, we directly compared these two transcriptomes in order to obtain a list of genes enriched in GABA neurons compared with dopamine neurons. Next, we created a novel bioinformatic approach, that used the PANTHER (Protein ANalysis THrough Evolutionary Relationships) gene ontology database and VTA gene expression data from the Allen Mouse Brain Atlas, from which we obtained 6 candidate genes: Cbln4, Rxfp3, Rora, Gpr101, Trh and Nrp2. As a final step, we verified the selective expression of these candidate genes in sub-groups of GABA neurons in the VTA (and neighbouring substantia nigra pars compacta) using immunolabelling. Taken together, our study provides a valuable toolbox for the future investigation of GABA neuron sub-groups in the VTA.

Identifiants

pubmed: 31374129
doi: 10.1111/ejn.14534
pmc: PMC6972656
doi:

Substances chimiques

gamma-Aminobutyric Acid 56-12-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3732-3749

Subventions

Organisme : Medical Research Council
ID : MC_U120085816
Pays : United Kingdom

Informations de copyright

© 2019 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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Auteurs

Eleanor J Paul (EJ)

MRC London Institute of Medical Sciences (LMS), London, UK.
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.

Kyoko Tossell (K)

MRC London Institute of Medical Sciences (LMS), London, UK.
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.

Mark A Ungless (MA)

MRC London Institute of Medical Sciences (LMS), London, UK.
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.

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Classifications MeSH