Heterogeneous somatostatin-expressing neuron population in mouse ventral tegmental area

  1. Elina Nagaeva
  2. Ivan Zubarev
  3. Carolina Bengtsson Gonzales
  4. Mikko Forss
  5. Kasra Nikouei
  6. Elena de Miguel
  7. Lauri Elsilä
  8. Anni-Maija Linden
  9. Jens Hjerling-Leffler
  10. George J Augustine
  11. Esa R Korpi  Is a corresponding author
  1. University of Helsinki, Finland
  2. Aalto University, Finland
  3. Karolinska Insitutet, Sweden
  4. Karolinska Institutet, Sweden
  5. Nanyang Technological University, Singapore

Abstract

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.

Data availability

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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Elina Nagaeva

    Department of Pharmacology, University of Helsinki, University of Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2828-6234
  2. Ivan Zubarev

    Neuroscience and Biomedical Engineering, Aalto University, Espoo, Finland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1620-8485
  3. Carolina Bengtsson Gonzales

    Department of Medical Biochemistry and Biophysics, Karolinska Insitutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Mikko Forss

    Department of Pharmacology, University of Helsinki, University of Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  5. Kasra Nikouei

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Elena de Miguel

    Department of Pharmacology, University of Helsinki, University of Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  7. Lauri Elsilä

    Department of Pharmacology, University of Helsinki, University of Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9744-4753
  8. Anni-Maija Linden

    Department of Pharmacology, University of Helsinki, University of Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  9. Jens Hjerling-Leffler

    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  10. George J Augustine

    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  11. Esa R Korpi

    Department of Pharmacology, University of Helsinki, University of Helsinki, Finland
    For correspondence
    esa.korpi@helsinki.fi
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0683-4009

Funding

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.

Reviewing Editor

  1. Olivier J Manzoni, Aix-Marseille University, INSERM, INMED, France

Ethics

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).

Version history

  1. Received: May 26, 2020
  2. Accepted: August 1, 2020
  3. Accepted Manuscript published: August 4, 2020 (version 1)
  4. Version of Record published: August 20, 2020 (version 2)

Copyright

© 2020, Nagaeva et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Elina Nagaeva
  2. Ivan Zubarev
  3. Carolina Bengtsson Gonzales
  4. Mikko Forss
  5. Kasra Nikouei
  6. Elena de Miguel
  7. Lauri Elsilä
  8. Anni-Maija Linden
  9. Jens Hjerling-Leffler
  10. George J Augustine
  11. Esa R Korpi
(2020)
Heterogeneous somatostatin-expressing neuron population in mouse ventral tegmental area
eLife 9:e59328.
https://doi.org/10.7554/eLife.59328

Share this article

https://doi.org/10.7554/eLife.59328

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