Oligodendrocytes and myelin limit neuronal plasticity in visual cortex

• 成果类型: Article
• 署名作者: Xin, Wendy; Kaneko, Megumi; Roth, Richard H.; Zhang, Albert; Nocera, Sonia; Ding, Jun B.; Stryker, Michael P.; Chan, Jonah R.
• 署名单位: University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Stanford University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5894
• DOI: 10.1038/s41586-024-07853-8
• 发表日期: 2024-09-26
• 关键词: ocular dominance plasticity; monocular deprivation; cortical plasticity; dendritic spines; DYNAMICS; lineage

摘要

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 age2-4. 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. Through genetic blocking of oligodendrocyte differentiation and myelination in adolescent mice, we demonstrate that oligodendrocytes have a critical role in shaping the maturation and stabilization of visual cortical circuits.