Developmental oligodendrocytes regulate brain function through the mediation of synchronized spontaneous activity

Synchronized spontaneous neural activity is a fundamental feature of developing central nervous systems, hypothesized to be critical for brain development. However, the mechanisms regulating this synchronization and its long-term functional implications remain poorly understood. Here, we unveil a novel role for oligodendrocytes in orchestrating synchronized spontaneous activity during a critical developmental window, with profound consequences for adult brain function. Using cell-specific genetic manipulation in the mouse cerebellum, we demonstrate that oligodendrocyte deficiency during early postnatal development, but not after weaning, disrupts the synchronization of Purkinje cell activity in both developmental and adult stages. These early disruption of oligodendrocytes and neural synchrony resulted in persistent alterations in adult cerebellar-dependent behaviors, including anxiety, sociality, and motor function. Our findings establish a causal link between developmental oligodendrocyte-regulated neural synchrony and the emergence of complex brain functions. This study ensures the proper developmental trajectory necessary for driving brain function and opens new avenues for understanding neurodevelopmental disorders.