Bidirectional Optogenetic Modulations of Peripheral Sensory Nerve Activity: Induction vs. Suppression through Channelrhodopsin and Halorhodopsin

Abstract

In this study, we investigated the potential of optogenetics for modulating activity of peripheral sensory nerves, particularly tactile and proprioceptive afferents, which are vital for movement control. Using adeno-associated virus serotype 9 vector, we selectively transduced channelrhodopsin (ChR2) and halorhodopsin (eNpHR3.0) into large-diameter sciatic nerve afferents of rats. Diverging from conventional dorsal root ganglion (DRG) approaches, we applied optical stimulation at the distal portion of the afferent nerve. The intensity of optical stimulation varied to modulate the extent of induction and suppression of afferent activity. Then, the effect of optical stimulation was determined by the activity recorded in the dorsal root of the same afferents. Our findings show successful induction and suppression of activity in large-diameter afferents via optical stimulation. By increasing the intensity of blue (for ChR2) and yellow (for eNpHR3.0) light stimulation, the activity of fast-conducting afferent fibers was preferentially evoked or inhibited in an intensity-dependent manner. These data indicate that the activity of large-diameter afferents can systematically be regulated by optogenetics. The present innovative methodology for manipulating specific sensory modalities at the nerve level offers a targeted and accessible alternative to DRG stimulation, expanding the therapeutic scope of optogenetics for treating sensory disorders.