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Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):E321-8. doi: 10.1073/pnas.1419099112. Epub 2015 Jan 5.

Acceleration of conduction velocity linked to clustering of nodal components precedes myelination.

Author information

1
Sorbonne Universités Université Pierre et Marie Curie University of Paris 06, UMR_S 1127, Institut du Cerveau et de la Moelle-Groupe Hospitalo-Universitaire Pitié-Salpêtrière, F-75013, Paris, France; INSERM U1127, F-75013, Paris, France; CNRS UMR7225, F-75013, Paris, France;
2
Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan; Japan Science and Technology Agency, Tokyo 102-8666, Japan;
3
Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 ASB, United Kingdom; and.
4
Sorbonne Universités Université Pierre et Marie Curie University of Paris 06, UMR_S 1127, Institut du Cerveau et de la Moelle-Groupe Hospitalo-Universitaire Pitié-Salpêtrière, F-75013, Paris, France; INSERM U1127, F-75013, Paris, France; CNRS UMR7225, F-75013, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013, Paris, France catherine.lubetzki@psl.aphp.fr nathalie.sol-foulon@upmc.fr.
5
Sorbonne Universités Université Pierre et Marie Curie University of Paris 06, UMR_S 1127, Institut du Cerveau et de la Moelle-Groupe Hospitalo-Universitaire Pitié-Salpêtrière, F-75013, Paris, France; INSERM U1127, F-75013, Paris, France; CNRS UMR7225, F-75013, Paris, France; catherine.lubetzki@psl.aphp.fr nathalie.sol-foulon@upmc.fr.

Abstract

High-density accumulation of voltage-gated sodium (Nav) channels at nodes of Ranvier ensures rapid saltatory conduction along myelinated axons. To gain insight into mechanisms of node assembly in the CNS, we focused on early steps of nodal protein clustering. We show in hippocampal cultures that prenodes (i.e., clusters of Nav channels colocalizing with the scaffold protein ankyrinG and nodal cell adhesion molecules) are detected before myelin deposition along axons. These clusters can be induced on purified neurons by addition of oligodendroglial-secreted factor(s), whereas ankyrinG silencing prevents their formation. The Nav isoforms Nav1.1, Nav1.2, and Nav1.6 are detected at prenodes, with Nav1.6 progressively replacing Nav1.2 over time in hippocampal neurons cultured with oligodendrocytes and astrocytes. However, the oligodendrocyte-secreted factor(s) can induce the clustering of Nav1.1 and Nav1.2 but not of Nav1.6 on purified neurons. We observed that prenodes are restricted to GABAergic neurons, whereas clustering of nodal proteins only occurs concomitantly with myelin ensheathment on pyramidal neurons, implying separate mechanisms of assembly among different neuronal subpopulations. To address the functional significance of these early clusters, we used single-axon electrophysiological recordings in vitro and showed that prenode formation is sufficient to accelerate the speed of axonal conduction before myelination. Finally, we provide evidence that prenodal clusters are also detected in vivo before myelination, further strengthening their physiological relevance.

KEYWORDS:

GABAergic neuron; conduction velocity; myelination; node of Ranvier; sodium channel

PMID:
25561543
PMCID:
PMC4311839
DOI:
10.1073/pnas.1419099112
[Indexed for MEDLINE]
Free PMC Article

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