Difference in axon diameter and myelin thickness between excitatory and inhibitory callosally projecting axons in mice

Kaustuv Basu, Shailesh Appukuttan, Rohit Manchanda, Attila Sik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Synchronization of network oscillation in spatially distant cortical areas is essential for normal brain activity. Precision in synchronization between hemispheres depends on the axonal conduction velocity, which is determined by physical parameters of the axons involved, including diameter, and extent of myelination. To compare these parameters in long-projecting excitatory and inhibitory axons in the corpus callosum, we used genetically modified mice and virus tracing to separately label CaMKIIα expressing excitatory and GABAergic inhibitory axons. Using electron microscopy analysis, we revealed that (i) the axon diameters of excitatory fibers (myelinated axons) are significantly larger than those of nonmyelinated excitatory axons; (ii) the diameters of bare axons of excitatory myelinated fibers are significantly larger than those of their inhibitory counterparts; and (iii) myelinated excitatory fibers are significantly larger than myelinated inhibitory fibers. Also, the thickness of myelin ensheathing inhibitory axons is significantly greater than for excitatory axons, with the ultrastructure of the myelin around excitatory and inhibitory fibers also differing. We generated a computational model to investigate the functional consequences of these parameter divergences. Our simulations indicate that impulses through inhibitory and excitatory myelinated fibers reach the target almost simultaneously, whereas action potentials conducted by nonmyelinated axons reach target cells with considerable delay.

Original languageEnglish
Article numberbhac329
Pages (from-to)4101–4115
Number of pages16
JournalCerebral Cortex
Volume33
Issue number7
Early online date7 Oct 2022
DOIs
Publication statusPublished - 1 Apr 2023

Bibliographical note

© The Author(s) 2022

Keywords

  • callosal axons
  • conduction velocity
  • impulse propagation
  • myelination
  • synchronization

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