Abstract
Adaptive social behavior enables an animal to distinguish threat-associated from safety-associated conspecifics. Failure to make this distinction may lead to social withdrawal and social anxiety, prominent symptoms of several neuropsychiatric disorders (Lissek et al., 2008, 2014; Beckers et al., 2023; Li et al., 2023). Although recent progress has been made in identifying the neural circuits underlying social memory behaviors that distinguish a familiar from novel conspecific (Hitti and Siegelbaum, 2014; Stevenson and Caldwell, 2014; Smith et al., 2016; Wu et al., 2021), the neural mechanisms that enable social memory for the discrimination of individuals based on past aversive experiences remain unknown (Padilla-Coreano et al., 2022). Here, we used a social fear conditioning paradigm that induced in both sexes robust behavioral discrimination of a conspecific associated with a footshock (CS+) from a non-reinforced interaction partner (CS-). Strikingly, chemogenetic or optogenetic silencing of hippocampal CA2 pyramidal neurons, which have been previously implicated in social novelty recognition memory, resulted in generalized avoidance fear behavior towards both the CS- and CS+. One-photon calcium imaging revealed that the accuracy with which CA2 representations discriminate the CS+ from the CS- animal was enhanced following social fear conditioning. Moreover the CA2 representations incorporated a generalized or abstract representation of social valence irrespective of conspecific identity and location. Thus, our results demonstrate, for the first time, that the same hippocampal CA2 subregion mediates social memories based on conspecific familiarity and social threat, through the incorporation of a representation of social valence into an initial representation of social identity.
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