Comparison of the Efficacy of Optogenetic Stimulation of Glia versus Neurons in Myelination

Abstract

Increasing evidence demonstrates that optogenetics contributes to the regulation of brain behavior, cognition, and physiology, particularly during myelination, potentially allowing for the bidirectional modulation of specific cell lines with spatiotemporal accuracy. However, the type of cell to be targeted, namely, glia vs neurons, and the degree to which optogenetically induced cell activity can regulate myelination during the development of the peripheral nervous system (PNS) are still underexplored. Herein, we report the comparison of optogenetic stimulation (OS) of Schwann cells (SCs) and motor neurons (MNs) for activation of myelination in the PNS. Capitalizing on these optogenetic tools, we confirmed that the formation of the myelin sheath was initially promoted more by OS of calcium translocating channelrhodopsin (CatCh)-transfected SCs than by OS of transfected MNs at 7 days in vitro (DIV). Additionally, the level of myelination was substantially enhanced even until 14 DIV. Surprisingly, after OS of SCs, > 91.1% +/- 5.9% of cells expressed myelin basic protein, while that of MNs was 67.8% +/- 6.1%. The potent effect of OS of SCs was revealed by the increased thickness of the myelin sheath at 14 DIV. Thus, the OS of SCs could highly accelerate myelination, while the OS of MNs only somewhat promoted myelination, indicating a clear direction for the optogenetic application of unique cell types for initiating and promoting myelination. Together, our findings support the importance of precise cell type selection for use in optogenetics, which in turn can be broadly applied to overcome the limitations of optogenetics after injury.