Saltatory Conduction along Myelinated Axons Involves a Periaxonal Nanocircuit

Charles C.H Cohen,Marko A Popovic,Jan Klooster,Marie-Theres Weil,Wiebke Möbius,Klaus-Armin Nave,Maarten H.P Kole

doi:10.1016/j.cell.2019.11.039

Abstract

SummaryThe propagation of electrical impulses along axons is highly accelerated by the myelin sheath and produces saltating or “jumping” action potentials across internodes, from one node of Ranvier to the next. The underlying electrical circuit, as well as the existence and role of submyelin conduction in saltatory conduction remain, however, elusive. Here, we made patch-clamp and high-speed voltage-calibrated optical recordings of potentials across the nodal and internodal axolemma of myelinated neocortical pyramidal axons combined with electron microscopy and experimentally constrained cable modeling. Our results reveal a nanoscale yet conductive periaxonal space, incompletely sealed at the paranodes, which separates the potentials across the low-capacitance myelin sheath and internodal axolemma. The emerging double-cable model reproduces the recorded evolution of voltage waveforms across nodes and internodes, including rapid nodal potentials traveling in advance of attenuated waves in the internodal axolemma, revealing a mechanism for saltation across time and space.

Highlights

Vertebrate axons are ensheathed by multiple compacted myelin membranes spirally wrapped around the axolemma between the nodes of Ranvier, forming the anatomical basis for the rapid and saltatory conduction of electrical impulses in peripheral and central nervous systems (Hartline and Colman, 2007)
The propagation of electrical impulses along axons is highly accelerated by the myelin sheath and produces saltating or ‘‘jumping’’ action potentials across internodes, from one node of Ranvier to the
We made patch-clamp and high-speed voltage-calibrated optical recordings of potentials across the nodal and internodal axolemma of myelinated neocortical pyramidal axons combined with electron microscopy and experimentally constrained cable modeling

Summary

Introduction

Vertebrate axons are ensheathed by multiple compacted myelin membranes spirally wrapped around the axolemma between the nodes of Ranvier, forming the anatomical basis for the rapid and saltatory conduction of electrical impulses in peripheral and central nervous systems (Hartline and Colman, 2007). In the equivalent circuit representation, the axon and myelin sheath form one tightly combined membrane without intermediary conducting pathways, here referred to as ‘‘single cable’’ (SC). Based on sharp-electrode intracellular recordings (Barrett and Barrett, 1982; Blight and Someya, 1985; Funch and Faber, 1984) and computer simulations (Arancibia-Carcamo et al, 2017; Blight, 1985; Dimitrov, 2005; Gow and Devaux, 2008; McIntyre et al, 2002; Richardson et al, 2000; Stephanova and Bostock, 1995; Young et al, 2013), it is thought that axial conduction may occur between the myelin sheath and axon membrane, in the fluid-filled periaxonal and paranodal spaces, forming thereby an equivalent circuit referred to as ‘‘double cable’’ (DC). Optical recordings of APs using voltage-sensitive dyes (VSDs) reveals a strikingly complex gradual pattern of onset latencies along the internodes and nodes (Popovic et al, 2011; Stuart and Palmer, 2006), which remains to be explained

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