Oligodendrocytes and myelin limit neuronal plasticity in visual cortex

• Published in: Nature (London) Vol. 633; no. 8031; pp. 856 - 863
• Main Authors: Xin, Wendy, Kaneko, Megumi, Roth, Richard H., Zhang, Albert, Nocera, Sonia, Ding, Jun B., Stryker, Michael P., Chan, Jonah R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.09.2024; Nature Publishing Group
• Subjects: 14; 14/1; 14/63; 14/69; 631/378/2596/1705; 631/378/87; 64; 64/110; 82; 82/51; 9/74; Adolescents; Animals; Cell death; Cell Differentiation; Child development; Critical period; Dendritic plasticity; Dendritic spines; Dendritic Spines - metabolism; Dendritic Spines - physiology; Deprivation; Developmental plasticity; Female; Functional morphology; Functional plasticity; Gates (circuits); Genetic engineering; Humanities and Social Sciences; Hypotheses; Male; Maturation; Mice; Mice, Inbred C57BL; Monocular vision; multidisciplinary; Myelin; Myelin Sheath - metabolism; Myelination; Neural plasticity; Neuronal Plasticity - physiology; Oligodendrocytes; Oligodendroglia - cytology; Oligodendroglia - metabolism; Oligodendroglia - physiology; Optic nerve; Postpartum period; Proteins; Science; Science (multidisciplinary); Sensory Deprivation - physiology; Spine; Synaptic plasticity; Synaptic transmission; Synaptic Transmission - physiology; Vision, Monocular - physiology; Visual cortex; Visual Cortex - cytology; Visual Cortex - growth & development; Visual Cortex - physiology; Visual deprivation; Visual pathways; Visual plasticity
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-024-07853-8

Developmental myelination is a protracted process in the mammalian brain 1 . One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age 2 – 4 . We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity 5 . 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.