Myelination of Axons Corresponds with Faster Transmission Speed in the Prefrontal Cortex of Developing Male Rats

Visual Abstract Myelination of prefrontal circuits during adolescence is thought to lead to enhanced cognitive processing and improved behavioral control. However, while standard neuroimaging techniques commonly used in human and animal studies can measure large white matter bundles and residual conduction speed, they cannot directly measure myelination of individual axons or how fast electrical signals travel along these axons. Here we focused on a specific population of prefrontal axons to directly measure conduction velocity and myelin microstructure in developing male rats. An in vitro electrophysiological approach enabled us to isolate monosynaptic projections from the anterior branches of the corpus callosum (corpus callosum-forceps minor, CCFM) to the anterior cingulate subregion of the medial prefrontal cortex (Cg1) and to measure the speed and direction of action potentials propagating along these axons. We found that a large number of axons projecting from the CCFM to neurons in Layer V of Cg1 are ensheathed with myelin between pre-adolescence [postnatal day (PD)15] and mid-adolescence (PD43). This robust increase in axonal myelination is accompanied by a near doubling of transmission speed. As there was no age difference in the diameter of these axons, myelin is likely the driving force behind faster transmission of electrical signals in older animals. These developmental changes in axonal microstructure and physiology may extend to other axonal populations as well, and could underlie some of the improvements in cognitive processing between childhood and adolescence.