Optogenetic activation of fiber-specific compound action potentials in the mouse vagus nerve

A major function of the nervous system is to transmit information between the body and the brain. The vagus nerve, also known as the tenth cranial nerve, is an important conduit for brain-body communication and has been identified as a focus of bioelectronic therapies. Current neuromodulation therapies, such as vagus nerve stimulation (VNS), lack fiber- and molecular-specificity as they involve electrical stimulation of the entire nerve bundle. This results in recruitment of fiber types based on electrical properties rather than molecular specificity. To better understand the contributions of different fiber subtypes in the vagus nerve, we utilized optogenetics to record light-evoked compound actions potentials (CAPs) in TRPV1-ChR2-YFP and ChAT-ChR2-YFP mice. We found that direct photostimulation of TRPV1-ChR2 on the vagus nerve evoked large amplitude CAPs, while the same light stimulation in ChAT-ChR2 mice produced smaller amplitude CAPs. We also found that the amplitude of light-evoked CAPs decreased at a higher photostimulation frequency (25 Hz). Our results show that fiber-specific activation of the sensory afferent and motor efferent pathways in the vagus nerve produce discrete evoked CAPs. This can be used to decipher different neurotransmitter contributions in vagus nerve signaling for both the afferent and efferent pathways, thereby opening an avenue for potential selective, fiber-specific neuromodulation of the vagus nerve.