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

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Synchronized spontaneous neural activity is a fundamental feature of developing central nervous systems and is thought to be essential for proper brain development. However, the mechanisms that regulate this synchronization and its long-term impact on brain function remain unclear. Here, we identify a previously unrecognized role of oligodendrocytes in orchestrating synchronized spontaneous activity during a critical developmental window, with lasting consequences for adult behavior. Using oligodendrocyte-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 both during development and in adulthood. The early disruption produced persistent deficits in cerebellar-dependent behaviors, including anxiety, sociality, and motor function. Optogenetic re-synchronization in adulthood restored motor and social functions but not anxiety-like behavior, demonstrating that reduced Purkinje cell synchrony specifically drives the motor and social impairments. Our findings establish a causal link between developmental oligodendrocyte-regulated neural synchrony and the emergence of complex brain functions, which depend on the proper developmental trajectory necessary for driving brain function.