Astrocyte Ca2+ activity regulates node of Ranvier length in the white matter

Abstract

Nodes of Ranvier generate action potentials along myelinated axons, but it is unclear whether they can modulate neural circuit function. Computer modelling previously predicted that adjusting node length can control axonal conduction speed1, but it is unknown whether mechanisms controlling nodal structure operate in the healthy brain. Here, in brain slices and in intact white matter tracts of live mice, we found that nodes elongate and shorten, while an overall stable mean node length is maintained. Changes in node length were only detected in nodes that were flanked by compact myelin sheaths and, in brains of juvenile mice, neuronal activity caused the nodes to elongate. This occurred via astrocyte Ca2+-mediated adenosine generation, targeting myelin sheath A2b receptors which raised oligodendrocyte cyclic AMP levels. This activated NKCC1 cotransporters present in the myelin of the paranodes flanking the nodes, the expression of which was higher in the brains of juvenile mice compared to adults. NKCC1 activation elevated the membrane conductance of the myelin sheaths and reduced the length of the paranodal ends of the internodes, which was associated with node elongation that is predicted to slow action potential propagation. Thus, nodal dynamics may continuously tune information flow along myelinated axons and drive activity-dependent white matter plasticity.