Journal
CELL
Volume 180, Issue 2, Pages 311-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.11.039
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Funding
- NEURON
- ERC [261114]
- National Multiple Sclerosis Society [RG 4924A1/1]
- Netherlands Organization for Scientific Research [NWO Vici 865.17.003]
- ERC Advanced Grant AxoGLIA
- ERC Advanced Grant MyeliNANO
- Cluster of Excellence
- DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany
- Electron Microscopy Centre Amsterdam (EMCA) of the Amsterdam UMC
- European Research Council (ERC) [261114] Funding Source: European Research Council (ERC)
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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.
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