Environmental enrichment during social isolation prevents behavioral impairments and morphological alterations of the midcingulate cortex in aggressive socially isolated mice.

Social isolation (SI) in rodents affects neuronal integrity and behavioral regulation. On the other hand, enriched environment (EE) has been reported to yield beneficial behavioral and neural effects in group-housed rodents. The midcingulate cortex (MCC) is a brain region that is increasingly implicated in socioemotional regulation; however, whether SI induces structural alterations in this region, and whether EE can mitigate such effects, remains unclear. In the present study, we examined the behavioral consequences of SI and the associated dendritic alterations in MCC pyramidal neurons. Furthermore, we evaluated the preventive potential of EE against SI-induced impairments. Adult male Swiss mice were housed for six weeks in grouped conditions, individually in standard conditions (SC isolated), or individually in an enriched environment (EE isolated) that contains sensory, motor, and cognitive stimuli. Behavioral assessments included aggression, sociability, and anxiety-like behavior. Subsequently, Golgi-Cox staining was used to quantify dendritic complexity and spine density in MCC pyramidal neurons. Our results showed that SI markedly increased aggression and anxiety-like behavior and reduced sociability. Importantly, it produced structural alterations in MCC, particularly reduced dendritic complexity and spine density, which point to this region as a structural target of SI. EE housing during SI attenuated behavioral alterations and preserved MCC dendritic structure, indicating a potential neuroprotective effect on neuronal morphology. These results provide new evidence that MCC is structurally vulnerable to SI and responsive to EE, which suggests that EE may be a valuable strategy to improve animal welfare and mitigate the impacts of prolonged SI.