Myelin Deficits Caused by Olig2 Deficiency Lead to Cognitive Dysfunction and Increase Vulnerability to Social Withdrawal in Adult Mice

Oligodendrocyte (OL) and myelin development are crucial for network integration and are associated with higher brain functions. Accumulating evidence has demonstrated structural and functional impairment of OLs and myelin in serious mental illnesses. However, whether these deficits contribute to the brain dysfunction or pathogenesis of such diseases still lacks direct evidence. In this study, we conditionally deleted Olig2 in oligodendroglial lineage cells (Olig2 cKO) and screened the behavioral changes in adult mice. We found that Olig2 ablation impaired myelin development, which further resulted in severe hypomyelination in the anterior cingulate cortex. Strikingly, Olig2 cKO mice exhibited an anxious phenotype, aberrant responses to stress, and cognitive deficits. Moreover, Olig2 cKO mice showed increased vulnerability to social avoidance under the mild stress of social isolation. Together,these results indicate that developmental deficits in OL and myelin lead to cognitive impairment and increase the risk of phenotypes reminiscent of mental illnesses.