Remyelination alters the pattern of myelin in the cerebral cortex

Jennifer Orthmann-Murphy, Cody L. Call, Gian Carlo Molina-Castro, Yu Chen Hsieh, Matthew N. Rasband, Peter A. Calabresi, Dwight E. Bergles

Research output: Contribution to journalArticle

Abstract

Destruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here we performed time lapse in vivo two photon imaging in somatosensory cortex of adult mice to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation. These longitudinal studies revealed that the pattern of myelination in cortex changed dramatically after regeneration, as new oligodendrocytes were formed in different locations and new sheaths were often established along axon segments previously lacking myelin. Despite the dramatic increase in axonal territory available, oligodendrogenesis was persistently impaired in deeper cortical layers that experienced higher gliosis. Repeated reorganization of myelin patterns in MS may alter circuit function and contribute to cognitive decline.

Original languageEnglish (US)
Article numbere56621
Pages (from-to)1-61
Number of pages61
JournaleLife
Volume9
DOIs
StatePublished - May 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Orthmann-Murphy, J., Call, C. L., Molina-Castro, G. C., Hsieh, Y. C., Rasband, M. N., Calabresi, P. A., & Bergles, D. E. (2020). Remyelination alters the pattern of myelin in the cerebral cortex. eLife, 9, 1-61. [e56621]. https://doi.org/10.7554/eLife.56621