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Somatostatin-expressing neurons in the ventral tegmental area innervate specific forebrain regions and are involved in the stress response

View ORCID ProfileElina Nagaeva, Annika Schäfer, View ORCID ProfileAnni-Maija Linden, View ORCID ProfileLauri V. Elsilä, View ORCID ProfileMaria Ryazantseva, View ORCID ProfileJuzoh Umemori, Ksenia Egorova, View ORCID ProfileEsa R. Korpi
doi: https://doi.org/10.1101/2023.01.06.522982
Elina Nagaeva
1Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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  • For correspondence: elina.nagaeva@helsinki.fi
Annika Schäfer
1Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Anni-Maija Linden
1Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Lauri V. Elsilä
1Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Maria Ryazantseva
2HiLife Neuroscience Center, University of Helsinki, Helsinki, Finland
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Juzoh Umemori
3Gene and Cell technology, A.I. Virtanen Institute for molecular science, University of Eastern Finland, Kuopio, Finland
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Ksenia Egorova
1Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Esa R. Korpi
1Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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  • For correspondence: elina.nagaeva@helsinki.fi
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Abstract

Expanding knowledge about the cellular composition of subcortical brain regions demonstrates large heterogeneity and differences from the cortical architecture. Recently, we described three subtypes of somatostatin-expressing (Sst) neurons in the mouse ventral tegmental area (VTA) and showed their local inhibitory action on the neighbouring dopaminergic neurons (Nagaeva et al., 2020). Here, we report that VTA Sst neurons also project far outside the VTA and innervate several forebrain regions that are mainly involved in the regulation of emotional behaviour. When we deleted these VTA Sst neurons several behaviours and drug effects were affected, such as home cage activity, sensitization of locomotor activity to morphine, fear conditioning responses, and reactions to inescapable stress of forced swimming, often in a sex-dependent manner. Interestingly, the majority of these Sst projecting neurons was found to express Vglut2 and Th, but not Dat. Together, these data demonstrate that VTA Sst neurons have their selective projection targets, which are distinct from the main targets of VTA dopamine neurons and involved in the regulation of a variety of behaviours mostly associated with the stress response. This, in turn, makes these VTA neurons a meaningful addition to the somatostatinergic system of the brain.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 06, 2023.
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Somatostatin-expressing neurons in the ventral tegmental area innervate specific forebrain regions and are involved in the stress response
Elina Nagaeva, Annika Schäfer, Anni-Maija Linden, Lauri V. Elsilä, Maria Ryazantseva, Juzoh Umemori, Ksenia Egorova, Esa R. Korpi
bioRxiv 2023.01.06.522982; doi: https://doi.org/10.1101/2023.01.06.522982
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Somatostatin-expressing neurons in the ventral tegmental area innervate specific forebrain regions and are involved in the stress response
Elina Nagaeva, Annika Schäfer, Anni-Maija Linden, Lauri V. Elsilä, Maria Ryazantseva, Juzoh Umemori, Ksenia Egorova, Esa R. Korpi
bioRxiv 2023.01.06.522982; doi: https://doi.org/10.1101/2023.01.06.522982

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