Social Reactivation of Fear Engrams Enhances Memory Recall

Summary For group-living species such as humans and rodents, conspecific interactions pervasively shape emotion 3–5, attention 6, and cognitive ability 7–10. Higher-order cognitive processes such as memory within a social brain are thus interlaced with social influences. Traditional laboratory rodent cages offer a limited but nonetheless rich multi-modal landscape of communication, including auditory calls 11–14, chemical signaling 15, 16, and tactile stimulation 17, 18. The absence of such social encounters in singly housed animals results in cognitive impairments and depression-like phenotypes 23, likely obscuring how the social brain has evolved to function. It is thus important to understand the relationship between social context and how individuals process memories. As social interaction recruits hippocampal 29 and amygdalar 30 circuitry that also serves as hubs for non-social memory traces24–28, we hypothesized that pre-existing ensembles in these regions can be modulated by social experiences and lead to changes in memory expression. Here we show that stressful social experiences enhance the recall of previously acquired fear memories in male but not female mice. Activity-dependent tagging of cells in the dentate gyrus (DG) during fear learning revealed that these ensembles were endogenously reactivated during the social experiences in males. These reactivated cells were shown to be functional components of engrams, as optogenetic stimulation of the cells active during the social experience in previously fear conditioned animals was sufficient to drive fear-related behaviors. Our findings suggest that social encounters can reactivate pre-existing DG engrams and thereby strengthen discrete memories.