Large‐scale electron microscopic volume imaging of interfascicular oligodendrocytes in the mouse corpus callosum

Abstract

Single oligodendrocytes produce myelin sheaths around multiple axons in the central nervous system. Interfascicular oligodendrocytes (IOs) facilitate nerve conduction, but their detailed morphologies remain largely unknown. In the present study, we three‐dimensionally reconstructed IOs in the corpus callosum of adult mouse using serial block face scanning electron microscopy. The cell bodies of IOs were morphologically polarized and extended thick processes from the cytoplasm‐rich part of the cell. Processes originating from the cell body of each IO can be classified into two types: one myelinates an axon without branching, while the other type branches and each branch myelinates a distinct axon. Myelin sheaths originating from a particular IO have biased thicknesses, wrapping axons of a limited range of diameters. Consistent with this finding, IOs transduced and visualized with a rabies viral vector expressing GFP showed statistically significant variation in their myelination patterns. We further reconstructed the sheath immediately adjacent to that derived from each of the analyzed IOs; the thicknesses of the pair of sheaths were significantly correlated despite emanating from different IOs. These results suggest that a single axon could regulate myelin sheath thicknesses, even if the sheaths are derived from distinct IOs. Collectively, our results indicate that the IOs have their own myelin profiles defined by myelin thickness and axonal diameter although axons may regulate thickness of myelin sheath.

HiDiver: A Suite of Methods to Merge Magnetic Resonance Histology, Light Sheet Microscopy, and Complete Brain Delineations

“…The advantage of joint LSM and super-resolution TDI is that we are better able to interpret the fine-structure resolved in Figs 4B and E compared to previous state-of-the-art work (e.g., figure 5C from [36]) In corpus callosum and other tracts. The fine strands are consistent with fascicles of myelinated axons that contrast with darker interfascicular callosal oligodendrocytes [37] [38] ( Fig 4B and E ). Some of the strands are nearly 1 mm long and have an apparent diameter of 15–30 μm.…”

The glial framework reveals white matter fiber architecture in human and primate brains

“…It is unknown how glial cells are distributed in regions of axon crossing—i.e., whether they are arranged in arrays of intersecting glial rows or randomly distributed. This question has notable biological implications ( 28 ): If the glial framework persists in regions of fiber crossing, this strengthens the assumption that the spatial organization of glial cells has functional implications, providing evidence that glial cells are tract-specific and are not shared across tracts. We found evidence supporting the persistence of the glial framework in regions of fiber crossing: First, our ability to obtain maps similar to those derived from PLI with only Nissl-stained images suggested that the glial framework is a brainwide feature.…”

“…The glial framework-the patterned spatial organization of glial cells in the white matter-has been described in only a handful of pathways, namely the rat fimbria (13), the mouse corpus callosum (28) and the vervet corpus callosum (29). Additionally, Pandya and Schmahmann (3) briefly mentioned the glial framework (which they call the "glial matrix") in the context of the ILF and the nearby tracts.…”

“…Complex architectures such as axon crossing are ubiquitous in the brain, estimated to occur in 60 to 90% of white matter voxels in a typical acquisition of diffusion MRI (26). To date, the glial framework has been explored in few studies, all of which focus on specific tracts in regions with a single fiber population (13,(27)(28)(29). It is unknown how glial cells are distributed in regions of axon crossing-i.e., whether they are arranged in arrays of intersecting glial rows or randomly distributed.…”

Heterogeneity and regulation of oligodendrocyte morphology

“…While many of these early oligodendrocyte lineage cells degenerate and are lost during development ( Hughes and Stockton, 2021 ), surviving cells differentiate into myelinating and matured oligodendrocytes expressing markers such as myelin basic protein (MBP) and myelin-associated oligodendrocytic basic protein (MOBP), and produce myelin sheathes around multiple axons localized at the vicinity of their extended processes. The extension of process could be primarily limited but not restricted to a small range; oligodendrocytes do not myelinate axons closest to cell body, as observed with intrafascicular oligodendrocytes in the white matter ( Tanaka et al, 2021 ).…”