Developmental myelination is a protracted process in the mammalian brain¹. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age^2,3,4. We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity⁵. During adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. To determine whether oligodendrocyte maturation in turn regulates neuronal plasticity, we genetically blocked oligodendrocyte differentiation and myelination in adolescent mice. In adult mice lacking adolescent oligodendrogenesis, a brief period of monocular deprivation led to a significant decrease in visual cortex responses to the deprived eye, reminiscent of the plasticity normally restricted to adolescence. This enhanced functional plasticity was accompanied by a greater turnover of dendritic spines and coordinated reductions in spine size following deprivation. Furthermore, inhibitory synaptic transmission, which gates experience-dependent plasticity at the circuit level, was diminished in the absence of adolescent oligodendrogenesis. These results establish a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of developmental myelination acting as a functional brake on neuronal plasticity.

发育性髓鞘形成是哺乳动物大脑中一个漫长的过程¹。关于少突胶质细胞成熟如此缓慢的一种理论认为，髓鞘形成可能会在动物年龄^2、3、4 时稳定神经元回路并调节神经元的可塑性。我们在视觉皮层中测试了这一理论，视觉皮层有一个明确定义的经验依赖性神经元可塑性的关键期⁵。在青春期，视觉体验调节了视觉皮层中少突胶质细胞的成熟速率。为了确定少突胶质细胞成熟是否反过来调节神经元可塑性，我们对青少年小鼠的少突胶质细胞分化和髓鞘形成进行了基因阻断。在缺乏青少年少突形成的成年小鼠中，短暂的单眼剥夺导致视觉皮层对被剥夺的眼睛的反应显着降低，让人想起通常仅限于青春期的可塑性。这种增强的功能性可塑性伴随着树突棘的更大更新和剥夺后脊柱大小的协调减小。此外，在没有青少年少突形成的情况下，抑制性突触传递（在回路水平上控制经验依赖性可塑性）减弱。这些结果确定了少突胶质细胞在塑造皮质回路的成熟和稳定中的关键作用，并支持发育髓鞘形成作为神经元可塑性的功能制动器的概念。