During development, oligodendrocytes contact and wrap neuronal axons with myelin. Similarly to neurons and synapses, excess myelin sheaths are produced and selectively eliminated, but how elimination occurs is unknown. Microglia, the resident immune cells of the central nervous system, engulf surplus neurons and synapses. To determine whether microglia also prune myelin sheaths, we used zebrafish to visualize and manipulate interactions between microglia, oligodendrocytes, and neurons during development. We found that microglia closely associate with oligodendrocytes and specifically phagocytose myelin sheaths. By using a combination of optical, genetic, chemogenetic, and behavioral approaches, we reveal that neuronal activity bidirectionally balances microglial association with neuronal cell bodies and myelin phagocytosis in the optic tectum. Furthermore, multiple strategies to deplete microglia resulted in oligodendrocytes maintaining excessive and ectopic myelin. Our work reveals a neuronal activity-regulated role for microglia in modifying developmental myelin targeting by oligodendrocytes.

在发育过程中，少突胶质细胞与髓磷脂接触并包裹神经元轴突。与神经元和突触相似，多余的髓鞘产生并选择性消除，但消除的方式尚不清楚。小胶质细胞是中枢神经系统的固有免疫细胞，吞没了多余的神经元和突触。为了确定小胶质细胞是否也修剪髓鞘，我们使用斑马鱼来可视化和操纵发育过程中小胶质细胞，少突胶质细胞和神经元之间的相互作用。我们发现小胶质细胞与少突胶质细胞，特别是吞噬细胞的髓鞘紧密相关。通过使用光学，遗传，化学和行为的方法的组合，我们揭示了神经元活动双向平衡与神经元细胞体和视神经皮层中的髓鞘吞噬作用的小胶质细胞协会。此外，耗竭小胶质细胞的多种策略导致少突胶质细胞维持过多和异位的髓磷脂。我们的工作揭示了神经胶质细胞在调节少突胶质细胞靶向发展的髓磷脂中的神经元活性调节作用。