Nodes of Ranvier during development and repair in the CNS

Abstract

Saltatory conduction of action potentials along myelinated axons depends on small unmyelinated axonal domains, the nodes of Ranvier, where voltage-gated sodium channels are concentrated. Our knowledge on the complex molecular composition of these axonal domains still accumulates, whereas mechanisms of nodal assembly, established in the peripheral nervous system, remain only partially understood in the central nervous system. Apart from their key role in accelerating conduction, novel results have suggested that nodal variations allow to finely tune axonal conduction speed, to meet information processing needs. In addition, through their multiple glial contacts, nodes now appear as key actors for neuro-glial interactions. In pathology, disorganization of axonal domains is involved in the pathophysiology of various neurological diseases. In multiple sclerosis, nodal and perinodal disruption upon demyelination, with subsequent changes of ion channels distribution leads to altered axonal conduction and integrity. Nodal clusters then reform, coincident -but also prior to -remyelination, allowing restoration of axonal conduction. Here, we will review the current knowledge on nodes of Ranvier organization and function in the central nervous system; then discuss their dynamic changes during demyelination and remyelination, highlighting their impact on neuronal physiology in health and diseases and the related therapeutic perspectives. Bullet points• Nodes of Ranvier allow high-speed, saltatory propagation of action potentials along myelinated fibers • Multiple mechanisms contribute to nodal proteins clustering in the central nervous system • Multiple glial contacts at the nodal surface suggest that CNS node might act as an axoglial hub, opening new perspectives of neuro-glia communication • Variations of nodes of Ranvier length and diameter allow to finely tune axonal conduction speed, to meet information processing needs at the network scale • Nodal domains might represent sites of axonal vulnerability in demyelinating diseases • Disruption of node of Ranvier and paranodal junctions in CNS demyelinating diseases is associated with Nav and Kv channels redistribution, impacting action potential propagation and axonal integrity.

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

“…An important role of myelin is to establish distinct axonal domains (recently reviewed in detail in Lubetzki et al, 2020a;Rasband and Peles, 2021). The myelinated regions of axons can be divided into subdomains; the internode (corresponding to the compacted region of myelin), the paranodes (where the outer loops of the myelin contact the axon), the node of Ranvier (the ∼1 µm gap between adjacent myelin internodes) and the juxtaparanode (the interface between the paranode and compact myelin, rich in potassium channels) ( Figure 1).…”

Expansion Revealing: Decrowding Proteins to Unmask Invisible Brain Nanostructures

“…To understand the biological context of these periodic Aβ nanostructures, we stained brain slices with antibodies against the ion channels Nav1.6 and Kv7.2. In myelinated axons, Kv7 potassium channels and voltage gated sodium (Nav) channels colocalize tightly with nodes of Ranvier periodically along axons, while Nav1.6 and Kv7.2 are diffusely distributed along unmyelinated axons (26). Additionally, Alzheimer's is associated with altered neuronal excitability and alterations in ion channels (27).…”

R-Ras GTPases Signaling Role in Myelin Neurodegenerative Diseases

“…Myelin sheaths are multilayered membranes that result from wrapping and compaction of the plasma membranes of OLs around axons [ 2 , 3 ]. Myelination facilitates the disposition of depolarization machinery in discontinuous zones between myelin sheaths known as nodes of Ranvier [ 4 , 5 ]. This organization guarantees that axonal membrane depolarization only occurs at discontinuous zones, resulting in a rapid and effective saltatory conduction of the nerve impulse through the axon, a feature believed to contribute to vertebrate evolution [ 6 , 7 , 8 ].…”