Abstract
Action potential timing is fundamental to information processing; however, its determinants are not fully understood. Here we report unexpected structural specializations in the Ranvier nodes and internodes of auditory brainstem axons involved in sound localization. Myelination properties deviated significantly from the traditionally assumed structure. Axons responding best to low-frequency sounds had a larger diameter than high-frequency axons but, surprisingly, shorter internodes. Simulations predicted that this geometry helps to adjust the conduction velocity and timing of action potentials within the circuit. Electrophysiological recordings in vitro and in vivo confirmed higher conduction velocities in low-frequency axons. Moreover, internode length decreased and Ranvier node diameter increased progressively along the distal axon segments, which simulations show was essential to ensure precisely timed depolarization of the giant calyx of Held presynaptic terminal. Thus, individual anatomical parameters of myelinated axons can be tuned to optimize pathways involved in temporal processing.
Highlights
Action potential timing is fundamental to information processing; its determinants are not fully understood
The diameter and internode length of globular bushy cells (GBCs) axons, which transmit information that passes through an extra synapse in the medial nucleus of the trapezoid body (MNTB) and provide inhibition to the MSO and LSO (Fig. 1a), are larger than those of the spherical bushy cells (SBCs) axons transmitting excitatory information
An analysis of the analogous interaural time differences (ITD)-processing circuit in birds suggests that a different anatomical tuning mechanism occurs: differences of axon diameter and internode length may tune different length branches of the same myelinated axons to provide the required action potentials (APs) arrival times[13,14]
Summary
Action potential timing is fundamental to information processing; its determinants are not fully understood. These concepts came from a theoretical analysis (tested against experimental data)[2], which assumed that the physical size of all parts of myelinated axons should scale together, so that L/D should be constant (empirically measured as B100 for the peripheral nervous system), as should g 1⁄4 d/D; a g-ratio of B0.6 was suggested to maximize the spread of signals between nodes (but the experimental value is 0.7–0.8, both in the peripheral nervous system and central nervous system (CNS)) It would be surprising if myelinated CNS axons were as structurally invariant as is commonly assumed because the shape and timing of action potentials (APs) play a crucial role in synaptic transmission, information processing, rhythm generation and plasticity[5,6,7,8,9], and variation of any of the geometrical parameters of myelinated axons could be used to tune their conduction speed and AP shape. We demonstrate a novel mechanism that promotes calyx depolarization: the internode length decreases and the node diameter increases progressively towards the presynaptic terminal, and our detailed simulations predict that these gradations are crucial for precisely timed depolarization of the calyx of Held
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