Oligodendrocytes and myelin limit neuronal plasticity in visual cortex

Wendy Xin (), Megumi Kaneko, Richard H. Roth, Albert Zhang, Sonia Nocera, Jun B. Ding, Michael P. Stryker and Jonah R. Chan ()
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Wendy Xin: University of California San Francisco
Megumi Kaneko: University of California San Francisco
Richard H. Roth: Stanford University
Albert Zhang: University of California San Francisco
Sonia Nocera: University of California San Francisco
Jun B. Ding: Stanford University
Michael P. Stryker: University of California San Francisco
Jonah R. Chan: University of California San Francisco

Nature, 2024, vol. 633, issue 8031, 856-863

Abstract: 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 age2–4. 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.

Date: 2024
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DOI: 10.1038/s41586-024-07853-8

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