RT Journal Article SR Electronic T1 Somatostatin-expressing neurons in the ventral tegmental area innervate specific forebrain regions and are involved in the stress response JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.01.06.522982 DO 10.1101/2023.01.06.522982 A1 Elina Nagaeva A1 Annika Schäfer A1 Anni-Maija Linden A1 Lauri V. Elsilä A1 Maria Ryazantseva A1 Juzoh Umemori A1 Ksenia Egorova A1 Esa R. Korpi YR 2023 UL http://biorxiv.org/content/early/2023/01/06/2023.01.06.522982.abstract AB 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 StatementThe authors have declared no competing interest.