Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons

Malavasi, Elise L.V.; Ghosh, Aniket; Booth, Daniel G; Zagnoni, Michele; Sherman, Diane L.; Brophy, Peter

doi:10.7554/elife.68089

Cited by 8 publications

(4 citation statements)

References 75 publications

(137 reference statements)

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“…It is known that hippocampal inhibitory axons can form pre-nodal clusters of Nav channels along premyelinated axons ( Bonetto et al, 2019 ; Freeman et al, 2015 ). At a later stage of development, such prenodes of Nav/Neurofascin/AnkyrinG may indicate positions for limiting myelin sheath extension ( Malavasi et al, 2021 ; Thetiot et al, 2020 ; Vagionitis et al, 2022 ). During development, components of the nodes of Ranvier accumulate adjacent to the ends of myelin sheaths to form heminodes prior to forming nodes.…”

Section: Discussionmentioning

confidence: 99%

A class-specific effect of dysmyelination on the excitability of hippocampal interneurons

Pinatel,

Pearlstein,

Bonetto

et al. 2023

eLife

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The role of myelination for axonal conduction is well-established in projection neurons but little is known about its significance in GABAergic interneurons. Myelination is discontinuous along interneuron axons and the mechanisms controlling myelin patterning and segregation of ion channels at the nodes of Ranvier have not been elucidated. Protein 4.1B is implicated in the organization of the nodes of Ranvier as a linker between paranodal and juxtaparanodal membrane proteins to the spectrin cytoskeleton. In the present study, 4.1B KO mice are used as a genetic model to analyze the functional role of myelin in Lhx6-positive parvalbumin (PV) and somatostatin (SST) neurons, two major classes of GABAergic neurons in the hippocampus. We show that 4.1B-deficiency induces disruption of juxtaparanodal K+ channel clustering and mislocalization of nodal or heminodal Na+ channels. Strikingly, 4.1B-deficiency causes loss of myelin in GABAergic axons in the hippocampus. In particular, stratum oriens SST cells display severe axonal dysmyelination and a reduced excitability. This reduced excitability is associated with a decrease in occurrence probability of small amplitude synaptic inhibitory events on pyramidal cells. In contrast, stratum pyramidale fast-spiking PV cells do not appear affected. In conclusion, our results indicate a class-specific effect of dysmyelination on the excitability of hippocampal interneurons associated with a functional alteration of inhibitory drive.

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Section: Discussionmentioning

confidence: 99%

A class-specific effect of dysmyelination on the excitability of hippocampal interneurons

Pinatel,

Pearlstein,

Bonetto

et al. 2023

eLife

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“…The formation of node like clusters along axons prior to myelination has been shown to participate to mature node formation 9,13,16 , some node-like clusters predefining mature nodes being thus potentially landmarks for future myelination pattern. Furthermore, these clusters may regulate myelination itself by their role in conduction modulation and myelin deposition guidance 8,9 .…”

Section: An Indirect Modulation Of Myelination and Neuronal Network B...mentioning

confidence: 99%

“…Functionally, node-like clusters have proved to accelerate axonal conduction velocity. They further participate in heminodal and mature node assembly and guide myelination initiation at their direct vicinity 8,9,13,16 . In the zebrafish, a subset of node-like clusters is thought to predefine mature nodes of Ranvier localization 13 , suggesting that they could be landmarks for axonal domain and myelination pattern organization.…”

Section: Introductionmentioning

confidence: 99%

“…; https://doi.org/10.1101/2024.03. 16.585168 doi: bioRxiv preprint nervous system (CNS) to promote coordinated activity and memory consolidation [29][30][31][32] . Of note, these previous studies explored how neuronal activity influences myelination and remyelination per se, but did not unravel its effects on axonal microdomain organization.…”

Section: Introductionmentioning

confidence: 99%

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Neuronal activity promotes axonal node-like clustering prior to myelination and remyelination in the central nervous system

Ronzano,

Perrot,

Mazuir

et al. 2024

Preprint

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Nodes of Ranvier ensure the fast saltatory conduction along myelinated axons, through their enrichment in voltage-gated sodium and potassium channels. We and others have shown that node-like cluster assembly can occur before myelination. In multiple sclerosis, demyelination is associated with node of Ranvier disassembly, but node-like reassembly can occur prior to remyelination. Given the crucial role of neuronal activity in inducing (re)myelination, we asked whether neuronal activity could regulate node-like clustering. We show that node-like clustering is promoted by neuronal activity and decreased when excitatory glutamatergic receptors are inhibited. Altering glutamatergic neurotransmission leads to the downregulation of Nav1.1 expression, which we show to be critical for node-like clustering. Neuronal activity also promotes node-like clustering in remyelination. As node-like clusters modulate conduction velocity and myelination initiation along axons, we propose that activity-dependent node-like clustering could modulate neuronal network establishment, as well as myelination regulation and patterning during development, plasticity and repair.

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Developmental shaping of node of Ranvier geometry contributes to spike timing maturation in primary auditory afferents

Smith,

Lezmy,

Arancibia-Cárcamo

et al. 2024

Cell Reports

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Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons

Cited by 8 publications

References 75 publications

A class-specific effect of dysmyelination on the excitability of hippocampal interneurons

A class-specific effect of dysmyelination on the excitability of hippocampal interneurons

Neuronal activity promotes axonal node-like clustering prior to myelination and remyelination in the central nervous system

Developmental shaping of node of Ranvier geometry contributes to spike timing maturation in primary auditory afferents

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