Astrocyte Ca ²⁺ activity regulates node of Ranvier length in the white matter

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 speed ¹ , 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 more motile nodes were observed as myelination progressed during development. In the developing brain, but not in adult mice, neuronal activity caused the nodes to elongate. This occurred via astrocyte Ca ²⁺ -mediated adenosine generation, targeting A _2b receptors expressed in myelin sheaths which raised cyclic AMP levels in oligodendrocytes. This activated NKCC1 cotransporters present in the myelin of the paranodes and internodes, the expression of which was upregulated in the developing brain compared to adults. NKCC1 activation elevated the membrane conductance and reduced the length of internodal myelin sheaths. Thus, nodal dynamics may continuously tune information flow along myelinated axons and drive activity-dependent white matter plasticity.