The Anterior BNST Is Required for Novelty-Driven Social Interaction

Abstract

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.