The cellular architecture of the ventral tegmental area (VTA), the main hub of the brain reward system, remains only partially characterized. To extend the characterization to inhibitory neurons, we have identified three distinct subtypes of somatostatin (Sst)-expressing neurons in the mouse VTA. These neurons differ in their electrophysiological and morphological properties, anatomical localization, as well as mRNA expression profiles. Importantly, similar to cortical Sst-containing interneurons, most VTA Sst neurons express GABAergic inhibitory markers, but some of them also express glutamatergic excitatory markers and a subpopulation even express dopaminergic markers. Furthermore, only some of the proposed marker genes for cortical Sst neurons were expressed in the VTA Sst neurons. Physiologically, one of the VTA Sst neuron subtypes locally inhibited neighboring dopamine neurons. Overall, our results demonstrate the remarkable complexity and heterogeneity of VTA Sst neurons and suggest that these cells are multifunctional players in the midbrain reward circuitry.
scRNA-seq raw and expression data have been deposited in the ArrayExpress database at EMBL-EBI (www.ebi.ac.uk/arrayexpress) under accession number E-MTAB-8780.The following previously published data sets were used:•https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE115746 (Tasic et al., 2018)•https://storage.googleapis.com/dropviz-downloads/static/regions/F_GRCm38.81.P60SubstantiaNigra.raw.dge.txt.gz (Saunders et al., 2018)Custom written software for automated firing pattern analysis is available for downloading from here: https://github.com/zubara/fffpa.
PatchSeq experiment on somatostatin-expressing (Sst) neurons from mouse ventral tegmental area (VTA). Full-length single cell sequencinghttps://www.ebi.ac.uk/E-MTAB-8780.
Shared and distinct transcriptomic cell types across neocortical areashttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE115746.
Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain10.1016/j.cell.2018.07.028.
The project was funded by the Academy of Finland (1278174 and 1317399), The Finnish National Agency for Education EDUFI, the Sigrid Juselius Foundation, and research grants MOE2015-T2-2-095 and MOE2017-T3-1-002 from the Singapore Ministry of Education. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animal experiments were authorized by the National Animal Experiment Board in Finland (Eläinkoelautakunta, ELLA; Permit Number: ESAVI/1172/04.10.07/2018) and Institutional Animal Care and Use Committee in Singapore (NTU-IACUC).
- Olivier J Manzoni, Aix-Marseille University, INSERM, INMED, France
© 2020, Nagaeva et al.
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