Further, we show that the myelinic channel system, while relatively stable, can undergo subtle dynamic shape changes over days. Together, these data lead us to propose a slightly revised model of the ‘unrolled’ 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 matter by Río-Hortega, despite that he questioned whether some cytoplasmic figures he observed represented artefact. 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. One hundred years later, we review his original contributions 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. 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.
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