Regulation of conduction time along axons

Abstract

Timely delivery of information is essential for proper functioning of the nervous system. Precise regulation of nerve conduction velocity is needed for correct exertion of motor skills, sensory integration and cognitive functions. In vertebrates, the rapid transmission of signals along nerve fibers is made possible by the myelination of axons and the resulting saltatory conduction in between nodes of Ranvier. Myelin is a specialization of glia cells and is provided by oligodendrocytes in the central nervous system. Myelination not only maximizes conduction velocity, but also provides a means to systematically regulate conduction times in the nervous system. Systematic regulation of conduction velocity along axons, and thus systematic regulation of conduction time in between neural areas, is a common occurrence in the nervous system. To date, little is understood about the mechanism that underlies systematic conduction velocity regulation and conduction time synchrony. Node assembly, internode distance (node spacing) and axon diameter - all parameters determining the speed of signal propagation along axons - are controlled by myelinating glia. Therefore, an interaction between glial cells and neurons has been suggested. This review summarizes examples of neural systems in which conduction velocity is regulated by anatomical variations along axons. While functional implications in these systems are not always clear, recent studies on the auditory system of birds and mammals present examples of conduction velocity regulation in systems with high temporal precision and a defined biological function. Together these findings suggest an active process that shapes the interaction between axons and myelinating glia to control conduction velocity along axons. Future studies involving these systems may provide further insight into how specific conduction times in the brain are established and maintained in development. Throughout the text, conduction velocity is used for the speed of signal propagation, i.e. the speed at which an action potential travels. Conduction time refers to the time it takes for a specific signal to travel from its origin to its target, i.e. neuronal cell body to axonal terminal.

Keywords: auditory system; coincidence detection; conduction velocity regulation; internode distance; neuronal isochronicity; neuron–glia interaction.

Figure 1

Figure Differential regulation of conduction velocity in two major branches of single axon Nucleus magnocellularis (NM) and nucleus laminaris (NL) embody a modified Jeffress model (Jeffress, 1948) where contralateral NM axons form a delay line on the ventral side of a NL cell line. This delay line sequentially slows down the contralaterally evoked sound signal and enables coincidence with the ipsilateral inputs that creates no delay between terminals. Depending on the ITD presented, coincident inputs occur at a different location in NL, rendering the NL cell line a map or sound source location along the azimuth (Carr and Konishi, 1990; Köppl and Carr, 2008). The ipsilateral and contralateral axon branches of the NM axon display a length difference of more than 1600 μm. Conduction velocities in the ipsilateral and contralateral branches are adjusted utilizing variations in internode distance and axon diameter so that conduction times achieve isochronicity in the microsecond range. In the shorter axon branch, internode distance and axon diameter are shorter and thinner, respectively, than in the longer axon branch. The differential regulation of conduction time in the sub-millisecond range between two major collaterals of a single axon to fulfill a well-described biological function is unprecedented (Seidl et al., 2010). Note that both axon segments are part of a single NM axon. Magenta, ipsilateral axon branch; green, contralateral axon branch; blue, myelin sheath.