A bottom-up reward pathway mediated by somatostatin neurons in the medial septum complex underlying appetitive learning.

Valence detection and processing are essential for the survival of animals and their life quality in complex environments. Neural circuits underlying the transformation of external sensory signals into positive valence coding to generate appropriate behavioral responses remain not well-studied. Here, we report that somatostatin (SOM) subtype of GABAergic neurons in the mouse medial septum complex (MS), but not parvalbumin subtype or glutamatergic neurons, specifically encode reward signals and positive valence. Through an ascending pathway from the nucleus of solitary tract and then parabrachial nucleus, the MS SOM neurons receive rewarding taste signals and suppress the lateral habenula. They contribute essentially to appetitive associative learning via their projections to the lateral habenula: learning enhances their responses to reward-predictive sensory cues, and suppressing their responses to either conditioned or unconditioned stimulus impairs acquisition of reward learning. Thus, MS serves as a critical hub for transforming bottom-up sensory signals to mediate appetitive behaviors.