LAUSR

In the mammalian brain, rapid conduction of neural information is supported by the myelin, whose functional efficacy shows steep dependence on its nanoscale cytoarchitecture. Although previous in vitro studies suggested that neural activity accompanies nanometer-scale cellular deformations, it has remained unexplored whether neural activity can dynamically remodel the myelinated axon due to the technical challenge in observing its nanostructural dynamics in living tissues. To this end, we introduced a novel all-optical approach combining a nanoscale dynamic readout based on spectral interferometry and optogenetic control of neural excitation on a living brain slice preparation. 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. In summary, our novel all-optical studies substantiate that myelinated axon exhibits activity-dependent nanoscale swelling, which potentially serves to dynamically tune the transmission speed of neural information. RESEARCH SUMMARIES As neural activity involves rapid ion flux across the cell membrane, researchers have long been tried to detect the accompanying nanoscale morphological dynamics. However, measuring the activity-dependent nanostructural dynamics in the living mammalian brain has been an enigma due to the technical limitations. By combining excitatory optogenetics and in situ nanoscale metrology based on spectral interference, we demonstrate the first direct observation that the mammalian axons exhibit transient activity-dependent swelling at subnanometer-scale.