Identification of the subventricular tegmental nucleus as brainstem reward center

Rewards are essential for motivation, decision-making, memory, and mental health. We identified the subventricular tegmental nucleus (SVTg) as a brainstem reward center. In mice, reward and its prediction activate the SVTg, and SVTg stimulation leads to place preference, reduced anxiety, and accumbal dopamine release. Mice self-stimulate the SVTg, which can also be activated directly by the neocortex, resulting in effective inhibition of the lateral habenula, a region associated with depression. This mechanism may also explain why SVTg suppression induces aversion and increases fear. The translational relevance of these findings is supported by evidence in the rat, monkey, and human brainstem, establishing SVTg as a key hub for reward processing, emotional valence, and motivation. Single cell RNA-sequencing on virally labelled SVTg GABAergic neurons collected from vGAT-Cre mice injected with AAVretro-EF1a-DIO-mCherry into bilateral LHb. The GN029 cell was excluded from further analysis because it did not express either the Cre enzyme or the mCherry gene.