White matter fiber bundles enable robust conduction and time-critical signaling despite axon caliber variation.

In 450,000 3D axon reconstructions from male rats, axon bundles show stable ensemble radius distributions despite along-axon caliber variation, enabling robust conduction velocity predictions.

• Why it matters: 2D histology assumes cylindrical axons with radius-based conduction, but 3D histology shows along-axon radius variability that could undermine those conduction estimates.
• What they did: The study analyzed 450,000 3D reconstructions to test whether 2D cross-sections capture bundle radius distributions and whether this supports conduction velocity prediction despite variability.
• The result: Along-axon variability had only a modest effect, with particularly stable conduction in large axons, supporting time-critical signaling and validating 2D sampling for 46 million human corpus callosum axons.