Activity-dependent structural plasticity of myelinated axons tunes their excitability

Abstract

While myelinated axons are classically viewed as fixed cables, recent evidence suggests that activity can rapidly alter their geometry. Here we examined how this occurs and its functional implications, by using two-photon imaging, excitability testing and axial conductance measurements in adult mouse spinal cords. We found that focal subthreshold stimulation thins the internode to about 70% of its diameter within seconds, sparing the node and paranode, while neighbouring glia swell to fill the vacated space. The thinned axon becomes markedly more excitable for hours, by the amount cable theory predicts from its shortened length constant. Thinning requires Kv1 channels under the myelin, Na/K-ATPase, bicarbonate and a local alkaline shift, and is reproduced and occluded by axonal GABAA receptor activation. Clinically used charge-balanced stimulation protocols drive the same change. Activity-dependent axon thinning therefore gives axons a structural memory of recent activity, and may underlie the lasting benefits of spinal cord stimulation.