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

Abstract

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.