Social novelty preference-the tendency to interact more with unfamiliar than familiar conspecifics-is conserved across species and disrupted in disorders such as autism spectrum disorder, schizophrenia, and social anxiety. While the hippocampus and related circuits are known to encode social recognition memory, the mechanisms that translate familiarity signals into behavioral differences remain unclear. Here, we show that male mice exhibit a robust preference for engaging with unfamiliar over familiar conspecifics. Using c-Fos labeling, RNAscope, immunohistochemistry, and fiber photometry, we found that inhibitory and DRD1-expressing neurons in the dorsal subdivision of the anterior bed nucleus of the stria terminalis (BNSTa) are broadly activated during social and novel-object interaction. However, chemogenetic inhibition of the BNSTa selectively suppressed interaction with unfamiliar conspecifics while leaving familiar and novel-object interactions unaffected. These findings identify the BNSTa as a critical node that promotes novelty-driven social engagement, revealing a circuit mechanism for social novelty preference. Because deficits in novelty processing are central to multiple neuropsychiatric disorders, our results highlight the BNST as a potential locus of dysfunction linking social recognition to behavior.Significance statement Recognizing whether a social partner is familiar or unfamiliar is fundamental for survival, yet most research has overlooked how familiarity shapes social behavior. Here we identify the anterior bed nucleus of the stria terminalis (BNSTa) as a critical regulator of interactions with unfamiliar conspecifics. Although BNSTa inhibitory neurons are broadly engaged during social encounters, chemogenetic inhibition selectively suppresses social engagement with strangers while leaving interactions with familiar conspecifics and objects intact. These findings reveal a previously unexplored role for the BNSTa in promoting novelty-driven social interaction. Because disruptions in social novelty processing are a hallmark of conditions such as autism spectrum disorder, schizophrenia, and social anxiety, our results provide insight into how BNST dysfunction may contribute to psychiatric social deficits.
Jacobs et al. (Wed,) studied this question.