Internal axonal cytoarchitecture is shaped locally by external compressive forces.

The cross-sectional architecture of the axon and the area of its surrounding Schwann cell were quantified at selected histological regions along the length of avian myelinated axons. The number of neurofilaments (NFs), the density of NFs, axoplasmic area, and Schwann cell cross-sectional area were measured. These parameters were examined at Schmidt-Lanterman (S-L) clefts, at paranodal-nodal regions, and at regions of compact myelin Schwann cell nuclei. The results were then compared with the same parameters in adjacent compact myelinated regions of the same axons. At S-L clefts, paranodal-nodal regions, and Schwann cell nuclei, the axonal areas were smaller and the NF densities were higher than at compact myelinated regions. From other studies, it has been suggested that NF organization is responsive to local compressive forces--NF packing density tends to increase with increasing compression of the axon. We found that the NF packing densities were relatively small and the axon diameters were relatively large in the compact myelinated regions; this result suggests that in these axonal regions external constraints on axonal architecture are minimal. The higher NF packing densities and smaller axon diameters in the other histological regions suggest that external compressive effects on the axon increase in the following order: simple compact myelin less than Schwann cell nucleus less than S-L cleft less than paranodal-nodal region. Ultrastructural comparisons of these 4 histological regions show that the Schwann cell cross-sectional areas differ reproducibly, and this is consistent with the idea that variations in the organization of extra-axonal elements that envelop the axon produce different amounts of physical constraint on the axon and that this can affect the amount of external pressure on the internal architecture of the axon.