美国加州大学Jonah R. Chan和Wendy Xin研究团队近日取得一项新成果。经过不懈努力，他们发现少突胶质细胞和髓鞘限制了视觉皮层神经元的可塑性。该研究于2024年8月21日发表于国际一流学术期刊《自然》杂志上。

课题组在视觉皮层中测试了这一理论，因为视觉皮层对于依赖经验的神经元可塑性有一个明确的关键期。在青春期，视觉经验调节了视觉皮层少突胶质细胞成熟的速度。为了确定少突胶质细胞的成熟是否反过来调节神经元的可塑性，研究团队在青春期小鼠中通过基因阻断少突胶质细胞的分化和髓鞘形成。

在缺乏青春期少突胶质发生的成年小鼠中，短暂的单眼剥夺导致视觉皮层对被剥夺眼睛的反应显著下降，让人想起通常仅限于青春期的可塑性。这种增强的功能可塑性伴随着更多的树突棘的更新和剥夺后脊柱尺寸的协调缩小。

此外，抑制突触传递在环路水平上抑制经验依赖的可塑性，在青少年少突胶质发生缺失的情况下减弱。这些结果确立了少突胶质细胞在形成皮层环路的成熟和稳定方面的关键作用，并支持了发育性髓鞘形成作为神经元可塑性功能制动器的概念。

研究人员表示，在哺乳动物的大脑中，髓鞘形成是一个漫长的过程。一种解释少突胶质细胞成熟如此缓慢的理论认为，随着动物年龄的增长，髓鞘形成可能会稳定神经元环路，并调节神经元的可塑性。

附：英文原文

Title: Oligodendrocytes and myelin limit neuronal plasticity in visual cortex

Author: Xin, Wendy, Kaneko, Megumi, Roth, Richard H., Zhang, Albert, Nocera, Sonia, Ding, Jun B., Stryker, Michael P., Chan, Jonah R.

Issue&Volume: 2024-08-21

Abstract: 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 age2,3,4. 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.

DOI: 10.1038/s41586-024-07853-8

Source: https://www.nature.com/articles/s41586-024-07853-8