Hippocampal dorsal and ventral CA2 enable social discrimination after acute social defeat

Remembering the valence of conspecifics based on past aggressive compared to non-aggressive interactions is important for proper adaptive social behaviors. How a single naturalistic encounter establishes a lasting memory of the valence of the experience remains unclear. Our recent work shows that the CA2 region in ventral hippocampus, unlike dorsal CA2, is not required for social novelty discrimination but does contribute with dorsal CA2 to promote social aggression. How CA2 contributes to valence-associated social memory across the dorsoventral axis remains unresolved. We developed an acute defeat-associated social threat discrimination memory (AD-STDM) paradigm after which a male mouse preferentially interacted with a familiar non-aggressor male compared to a familiar aggressor male 24 h after a single defeat episode. Chemogenetic inhibition of Avpr1b-expressing CA2 neurons in either dorsal or ventral hippocampus during learning impaired subsequent discrimination. Acute defeat also increased cFos expression in ventral CA2 neurons relative to non-aggressive social interaction. Thus, although ventral CA2 is not required for social novelty recognition memory, it is required for social memory of an aversive social experience, with a relatively greater level of neural activation during aversive compared to non-aversive social encounters. In contrast, dorsal CA2 is required for both non-aversive and aversive forms of social memory.