# Neuronal Activity Promotes Node‐Like Cluster Assembly Prior to Myelination and Remyelination in the Central Nervous System

**Authors:** Rémi Ronzano, Clément Perrot, Elisa Mazuir, Melina Thetiot, Marie‐Stéphane Aigrot, Paul Stheneur, François‐Xavier Lejeune, Bruno Stankoff, Catherine Lubetzki, Nathalie Sol‐Foulon, Anne Desmazières

PMC · DOI: 10.1002/glia.70138 · Glia · 2026-02-23

## TL;DR

Neuronal activity helps form node-like clusters before myelination, which may influence how nerves communicate and repair.

## Contribution

The study reveals that neuronal activity regulates node-like cluster formation through Nav1.1, a key step in activity-driven myelination.

## Key findings

- Neuronal activity promotes node-like cluster assembly before myelination and remyelination.
- Nav1.1 is essential for node-like cluster formation and is regulated by neuronal activity.
- Node-like clusters may serve as intermediates in shaping myelin patterns during development and repair.

## Abstract

In recent years, myelination has been recognized as a key process in neural plasticity and network refinement, in addition to its role in axonal conduction and neuronal metabolic support. The fast saltatory conduction along myelinated fibers relies on the nodes of Ranvier. Node‐like clusters can form prior to myelin deposition in development and repair and can regulate axonal conduction, myelin deposition initiation, as well as contribute to the formation of mature nodes of Ranvier. In this study, we show that node‐like cluster assembly is modulated by neuronal activity and could thus be an intermediate step in activity‐induced (re)myelination. We further identify the regulation of Nav1.1 expression, which we show to be required for node‐like cluster formation, as part of the molecular mechanism implicated in the activity‐dependent regulation of node‐like cluster assembly. This process may serve in shaping neuronal networks and myelin patterns during development, plasticity and repair.

Ronzano et al. show that neuronal activity promotes node‐like cluster (NLC) formation before (re)myelination by regulating β1Nav and Nav1.1, which are essential for NLC assembly. This may represent an intermediate step in activity‐driven myelination and contribute to the regulation of axonal conduction.

## Linked entities

- **Genes:** SCN1A (sodium voltage-gated channel alpha subunit 1) [NCBI Gene 6323]

## Full-text entities

- **Genes:** Pdgfa (platelet derived growth factor subunit A) [NCBI Gene 25266] {aka PDGF-1, PDGFACP}, Tf (transferrin) [NCBI Gene 24825] {aka Tfn, Trf}, Scn2a (sodium channel, voltage-gated, type II, alpha) [NCBI Gene 110876] {aka 6430408L10, A230052E19Rik, Nav1.2, Scn2a1}, Nrcam (neuronal cell adhesion molecule) [NCBI Gene 319504] {aka Bravo, C030017F07Rik, C130076O07Rik, mKIAA0343}, Scn10a (sodium channel, voltage-gated, type X, alpha) [NCBI Gene 20264] {aka Nav1.8, PN3, SNS}, Alb (albumin) [NCBI Gene 24186] {aka Alb1, Albza}, SST (somatostatin) [NCBI Gene 6750] {aka SMST, SST1}, Nfasc (neurofascin) [NCBI Gene 269116] {aka D430023G06Rik, NF, mKIAA0756}, Gpbar1 (G protein-coupled bile acid receptor 1) [NCBI Gene 227289] {aka BG37, GPCR, GPR131, M-BAR, TGR5}, Pcp2 (Purkinje cell protein 2 (L7)) [NCBI Gene 18545] {aka L7, Pcp-2}, Ocm (oncomodulin) [NCBI Gene 18261], GNAI1 (G protein subunit alpha i1) [NCBI Gene 2770] {aka Gi, HG1B, NEDHISB}, PVALB (parvalbumin) [NCBI Gene 5816] {aka D22S749}, Nodal (nodal growth differentiation factor) [NCBI Gene 18119] {aka Tg.413d}, Scn1a (sodium channel, voltage-gated, type I, alpha) [NCBI Gene 20265] {aka B230332M13, Nav1.1}, NODAL (nodal growth differentiation factor) [NCBI Gene 4838] {aka HTX5}, SCN1A (sodium voltage-gated channel alpha subunit 1) [NCBI Gene 6323] {aka DEE6, DEE6A, DEE6B, DRVT, EIEE6, FEB3}, Calb1 (calbindin 1) [NCBI Gene 12307] {aka Brain-2, CB, Calb, Calb-1}, Mir215 (microRNA 215) [NCBI Gene 387211] {aka Mirn215, mir-215, mmu-mir-215}, Cntnap1 (contactin associated protein-like 1) [NCBI Gene 53321] {aka Caspr, NCP1, Nrxn4, p190, shm}, RIC8B (RIC8 guanine nucleotide exchange factor B) [NCBI Gene 55188] {aka RIC8, hSyn}, Ank3 (ankyrin 3, epithelial) [NCBI Gene 11735] {aka 2900054D09Rik, Ank-3, AnkG, Ankyrin-3, Ankyrin-G}, Scn8a (sodium channel, voltage-gated, type VIII, alpha) [NCBI Gene 20273] {aka C630029C19Rik, NaCh6, Nav1.6, dmu, med, mnd-2}, Fos (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14281] {aka D12Rfj1, c-fos, cFos}, Mbp (myelin basic protein) [NCBI Gene 17196] {aka Hmbpr, golli-mbp, jve, mld, shi}, Grin1 (glutamate receptor, ionotropic, NMDA1 (zeta 1)) [NCBI Gene 14810] {aka GluN1, GluRdelta1, GluRzeta1, M100174, NMD-R1, NMDAR1}, Scn1b (sodium channel, voltage-gated, type I, beta) [NCBI Gene 20266], Kcna2 (potassium voltage-gated channel, shaker-related subfamily, member 2) [NCBI Gene 16490] {aka Akr6a4, Gm10672, Kca1-2, Kv1.2, Mk-2}, Kcnc1 (potassium voltage gated channel, Shaw-related subfamily, member 1) [NCBI Gene 16502] {aka C230009H10Rik, KShIIIB, KV4, Kcr2-1, Kv3.1, NGK2}
- **Diseases:** demyelinated (MESH:D003711), cytotoxicity (MESH:D064420), neuronal damage (MESH:D009410), MS (MESH:D009103), axonal injury (MESH:D001480), pain (MESH:D010146), neurodevelopmental psychiatric disorders (MESH:D001523), spinal cord lesion (MESH:D013118), Spinal Cord Demyelination (MESH:D020278)
- **Chemicals:** AMPA (MESH:D018350), DREADD (-), T4 (MESH:D013974), phenol-red (MESH:D010637), potassium (MESH:D011188), HEPES (MESH:D006531), penicillin (MESH:D010406), Na+ (MESH:D012964), Clozapine N-Oxide (MESH:C079149), sodium selenite (MESH:D018038), putrescine (MESH:D011700), oil (MESH:D009821), HCO3 - (MESH:D001639), L-glutamine (MESH:D005973), CO2 (MESH:D002245), Quisqualic acid (MESH:D016318), NBQX (MESH:C062865), LPC (MESH:D008244), buprenorphine (MESH:D002047), APV (MESH:C095108), T3 (MESH:D014284), DMSO (MESH:D004121), D-Glucose (MESH:D005947), NaCl (MESH:D012965), cuprizone (MESH:D003471), KYN (MESH:D007736), polyethylenimine (MESH:D011094), streptomycin (MESH:D013307), NMDA (MESH:D016202), progesterone (MESH:D011374), TTX (MESH:D013779), GlutaMax (MESH:C054122), VP (MESH:C038467)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929708/full.md

## References

79 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929708/full.md

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Source: https://tomesphere.com/paper/PMC12929708