A NOVEL BRAINSTEM REWARD CENTRE INDUCES REWARD-SEEKING BEHAVIOR

The lateral habenula (LHb) is a key regulatory center for the processing of negative experiences and adaptive decision-making, integrating sensory and experience-related information to modulate motivational and cognitive processes. Although the LHb is extensively connected with hindbrain regions, the functional significance of its brainstem inputs remains poorly understood. Using viral tracing approaches in transgenic mice, we labeled all inhibitory inputs to the LHb and identified a previously unrecognized gamma-aminobutyric acid (GABA)-ergic cell population in the pontine central gray. We termed this newly identified structure the subventricular tegmental nucleus (SVTg). Optogenetic behavioral experiments revealed that stimulation of the SVTg induced place preference, whereas inhibition elicited place avoidance. Furthermore, mice robustly self-stimulated their SVTg, indicating a role for this nucleus in reward-seeking behavior. SVTg activation also reduced anxiety-like behavior in the elevated plus maze and attenuated fear responses during contextual fear conditioning. Using cell type–specific retrograde rabies virus tracing, we demonstrated that the SVTg receives inputs from pontine, midbrain, and cortical regions. Focusing on cortical connectivity, stimulation of orbitofrontal cortex projections to the SVTg similarly induced place preference. Together, these findings identify a novel GABAergic pontine nucleus that plays a critical role in modulating negative experiences and reward-related behaviors, with potential implications in the pathophysiology of anxiety-related disorders.