Oxytocin receptor signaling in the dorsal lateral septum is essential for social transmission of food preference in mice

Abstract

Social learning is a fundamental adaptive strategy that critically shapes decision-making and feeding behaviors. Through the social transmission of food preference (STFP), animals acquire information about food safety via social interactions, forming a food-odor memory that overrides innate preferences and guides subsequent food preferences. However, the neural mechanisms through which social cues durably influence feeding preferences remain unclear. Here, we identify the lateral septum (LS) as a key node in STFP. We show that LS neuronal activity increases following social learning and reliably distinguishes between socially cued and uncued foods. Chemogenetic inhibition of the dorsal LS (dLS), but not the ventral LS (vLS), abolishes STFP-driven food preference, revealing subregional specificity within the LS. Furthermore, oxytocin receptor (OXTR) signaling within the dLS is required for STFP in mice, where it enhances neuronal excitability through PLC pathway activation. Together, our results reveal a subregion-specific circuit mechanism through which the dLS integrates social information with feeding motivation, and highlight oxytocinergic modulation as a key mediator of socially guided food preferences.