Adolescent oligodendrogenesis and myelination restrict experience-dependent neuronal plasticity in adult visual cortex

Abstract

BACKGROUNDDevelopmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age. We tested this hypothesis in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity.OBJECTIVES/METHODSTo prevent myelin progression, we conditionally deleted Myrf, a transcription factor necessary for oligodendrocyte maturation, from oligodendrocyte precursor cells (Myrf cKO) in adolescent mice. To induce experience-dependent plasticity, adult control and Myrf cKO mice were monocularly deprived by eyelid suture. Functional and structural neuronal plasticity in the visual cortex were assessed in vivo by intrinsic signal optical imaging and longitudinal two photon imaging of dendritic spines, respectively.RESULTSDuring adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. Myrf deletion from oligodendrocyte precursors during adolescence led to inhibition of oligodendrocyte maturation and myelination that persisted into adulthood. Following monocular deprivation, visual cortex activity in response to visual stimulation of the deprived eye remained stable in adult control mice, as expected for post-critical period animals. By contrast, visual cortex responses to the deprived eye decreased significantly following monocular deprivation in adult Myrf cKO mice, reminiscent of the plasticity observed in adolescent mice. Furthermore, visual cortex neurons in adult Myrf cKO mice had fewer dendritic spines and a higher level of spine turnover. Finally, monocular deprivation induced spatially coordinated spine size decreases in adult Myrf cKO, but not control, mice.CONCLUSIONSThese results demonstrate a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of myelin acting as a brake on neuronal plasticity during development.

Glial regulation of critical period plasticity

“…Astrocytes and oligodendrocytes are both born late in embryonic development, and oligodendrocyte maturation similarly mirrors the transition from critical period plasticity to stability. Indeed, a recent study found that blocking oligodendrocyte maturation was sufficient to extend ocular dominance plasticity ( Xin et al, 2023 ). While astrocytes mediate critical period closure through modulation of E/I balance and ECM composition, oligodendrocytes seem to function in parallel to ensure critical period closure.…”