An extensive literature details deterioration of multiple brain functions, especially memory and learning, during aging in humans and in rodents. In contrast, the decline of social functions is less well understood. It is presently not clear whether age-dependent deficits observed in social behavior mainly reflect the disruption of social networks activity or are simply secondary to a more general impairment of cognitive and executive functions in older individuals. To address this issue, we carried out a battery of behavioral tasks exploring different brain functions in young (3 months) and middle-aged wild-type mice (9 months). Consistent with previous reports, our results show no obvious differences between these two groups in most of the domains investigated including learning and memory. Surprisingly, in social tasks, middle-aged animals showed significantly reduced levels of interactions when exposed to a new juvenile mouse. In the absence of overt cognitive decline, our findings suggest that social impairments may precede the disruption of other brain functions and argue for a selective vulnerability of social circuits during aging.

Summary An extensive body of evidence supports the notion that exposure to an enriched/impoverished environment alters brain functions via epigenetic changes. However, how specific modifications of social environment modulate brain functions remains poorly understood. To address this issue, we investigate the molecular and behavioral consequences of briefly manipulating social settings in young and middle-aged wild-type mice. We observe that, modifications of the social context, only affect the performance in socially related tasks. Social enrichment increases sociability whereas isolation leads to the opposite effect. Our work also pointed out specific miRNA signatures associated to each social environment. These miRNA alterations are reversible and found selectively in the medial prefrontal cortex. Finally, we show that miRNA modifications linked to social enrichment or isolation might target rather different intracellular pathways. Together, these observations suggest that the prefrontal cortex may be a key brain area integrating social information via the modification of precise miRNA networks.