Abstract
SIGNIFICANCE: In the mammalian brain, rapid conduction of neural information is supported by the myelin, the functional efficacy of which shows steep dependence on its nanoscale cytoarchitecture. Although previous in vitro studies have suggested that neural activity accompanies nanometer-scale cellular deformations, whether neural activity can dynamically remodel the myelinated axon has remained unexplored due to the technical challenge in observing its nanostructural dynamics in living tissues. AIM: We aim to observe activity-dependent nanostructural dynamics of myelinated axons in a living brain tissue. APPROACH: We introduced a novel all-optical approach combining a nanoscale dynamic readout based on spectral interferometry and optogenetic control of neural excitation in an acute brain slice preparation. RESULTS: In response to optogenetically evoked neuronal burst firing, the myelinated axons exhibited progressive and reversible spectral redshifts, corresponding to the transient swelling at a subnanometer scale. We further revealed that the activity-dependent nanostructural dynamics was localized to the paranode. CONCLUSIONS: Our all-optical studies substantiate that myelinated axon exhibits activity-dependent nanoscale swelling, which potentially serves to dynamically tune the transmission speed of neural information.