All-optical observation on activity-dependent nanoscale dynamics of myelinated axons

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 activitydependent nanoscale swelling, which potentially serves to dynamically tune the transmission speed of neural information. (c) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Automated summary

This study aims to observe the activity-dependent nanostructural dynamics of myelinated axons in living brain tissue. Using a novel all-optical approach, researchers found that myelinated axons exhibit nanoscale swelling in response to neural activity, potentially contributing to the tuning of neural information transmission speed.