Bidirectional optogenetic modulation of peripheral sensory nerve activity: Induction vs. suppression through channelrhodopsin and halorhodopsin

iScience. 2025 Mar 26;28(4):112178. doi: 10.1016/j.isci.2025.112178. eCollection 2025 Apr 18.

ABSTRACT

In this study, we investigated the potential of optogenetics for modulating activity of peripheral sensory nerves, particularly tactile and proprioceptive afferents. Using adeno-associated virus serotype 9 vector, we selectively transduced channelrhodopsin (ChR2(H134R)) 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 nerve. Results show successful induction and suppression of activity in large-diameter afferents via optical stimulation. By increasing the intensity of blue (for ChR2(H134R)) and yellow (for eNpHR3.0) light stimulation, the activity of fast-conducting afferent fibers was preferentially evoked or inhibited in an intensity-dependent manner. This indicates 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.

PMID:40463961 | PMC:PMC12131270 | DOI:10.1016/j.isci.2025.112178