Oligodendrocytes and myelin limit neuronal plasticity in visual cortex

Nature. 2024 Sep;633(8031):856-863. doi: 10.1038/s41586-024-07853-8. Epub 2024 Aug 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 age2-4. 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.

MeSH terms

  • Animals
  • Cell Differentiation
  • Dendritic Spines* / metabolism
  • Dendritic Spines* / physiology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myelin Sheath* / metabolism
  • Neuronal Plasticity* / physiology
  • Oligodendroglia* / cytology
  • Oligodendroglia* / metabolism
  • Oligodendroglia* / physiology
  • Sensory Deprivation / physiology
  • Synaptic Transmission / physiology
  • Vision, Monocular / physiology
  • Visual Cortex* / cytology
  • Visual Cortex* / growth & development
  • Visual Cortex* / physiology