Oligodendrocyte dependent synchronized activity orchestrates circuit maturation and brain functionalization

Immature animals have the ability to interact with their environment, indicating that complex neural circuits are formed through mechanisms of self-organization. Correlated spontaneous activity among neurons suggests a universal principle behind the self-organization of complex neural circuits(1, 2), though the underlying mechanisms and functional roles in the central nervous system remain unclear. Here, we show that oligodendrocyte-dependent synchronized spontaneous activity during the critical period is indispensable for neural circuit refinement and brain functionalization. We found that oligodendrocyte deletion during specific time window disrupts Purkinje cell activity synchrony and synapse elimination in the mouse cerebellum. We further demonstrated that synchronized spontaneous activity is a prerequisite for synapse elimination. Behavioral analyses linked these developmental disruptions to adult cerebellar function, manifesting as anxiety-like behavior, reduced social interaction, and compromised motor coordination in adult mice. This association indicates the significance of following the appropriate developmental trajectory to ensure the integrity of brain function, suggesting that oligodendrocytes during development are vital organizers of brain functionalization. Our findings highlight the crucial role of oligodendrocytes in orchestrating synapse elimination and optimizing brain function through the mediation of synchronized activity during specific developmental stages.