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Abstract

A century ago this year, Pío del Río-Hortega (1921) coined the term ‘oligodendroglia’
for the ‘interfascicular glia’ with very few processes, launching an extensive discovery
effort on his new cell type. One hundred years later, we review his original contribu-
tions to our understanding of the system of cytoplasmic channels within myelin in the
context of what we observe today using light and electron microscopy of genetically
encoded fluorescent reporters and immunostaining. We use the term myelinic channel
system to describe the cytoplasm-delimited spaces associated with myelin; being the
paranodal loops, inner and outer tongues, cytoplasm-filled spaces through compact
myelin and further complex motifs associated to the sheath. Using a central nervous
system myelinating cell culture model that contains all major neural cell types and
produces compact myelin, we find that td-tomato fluorescent protein delineates the
myelinic channel system in a manner reminiscent of the drawings of adult white mat -
ter by Río-Hortega, despite that he questioned whether some cytoplasmic figures
he observed represented artefact. Together, these data lead us to propose a slightly
revised model of the ‘unrolled’ sheath. Further, we show that the myelinic channel
system, while relatively stable, can undergo subtle dynamic shape changes over days.
Importantly, we capture an under-appreciated complexity of the myelinic channel sys-
tem in mature myelin sheaths.