Saltatory Conduction along Myelinated Axons Involves a Periaxonal Nanocircuit

• Published in: Cell Vol. 180; no. 2; pp. 311 - 322.e15
• Main Authors: Cohen, Charles C.H., Popovic, Marko A., Klooster, Jan, Weil, Marie-Theres, Möbius, Wiebke, Nave, Klaus-Armin, Kole, Maarten H.P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.01.2020; Cell Press
• Subjects: action potential; action potentials; Action Potentials - physiology; Animals; axon; axons; Axons - metabolism; Axons - physiology; circuit; computational modelling; double cable; electric potential difference; electron microscopy; electronic circuits; internode; internodes; Male; Models, Neurological; myelin; myelin sheath; Myelin Sheath - physiology; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - physiology; Patch-Clamp Techniques - methods; periaxonal space; Pyramidal Cells - physiology; Ranvier's Nodes - physiology; Rats; Rats, Wistar; saltatory conduction; single cable; myelin; circuit; single cable; internode; computational modelling; axon; saltatory conduction; action potential; periaxonal space; double cable
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2019.11.039

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 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. [Display omitted] •Cable modeling reveals myelin and submyelin parameters consistent with EM•The periaxonal space is conductive and partially sealed at the paranodes•Optically recorded Vm confirms the separation of axon and myelin circuits•Double-cable internodes produce both temporal and amplitude saltation in Vm Patch-clamp recording and computational modeling combined with high-speed voltage-calibrated optical recordings and EM analysis reveal a second longitudinal conducting pathway formed by the periaxonal and paranodal submyelin spaces that are integral to reproducing the spatiotemporal profile of action potential saltation.