Feasibility and effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) in awake mice

Aims: Transcutaneous auricular vagus nerve stimulation (taVNS) is widely used to treat a variety of disorders because it is noninvasive, safe, and well tolerated by awake patients. However, long- term and repetitive taVNS is difficult to achieve in awake mice. Therefore, developing a new taVNS method that fully mimics the method used in clinical settings and is well-tolerated by awake mice is greatly important for general-izing research findings related to the effects of taVNS. The study aimed to develop a new taVNS device for use in awake mice and to test its reliability and effectiveness. Methods: We demonstrated the reliability of this taVNS device through retrograde neurotropic pseudorabies virus (PRV) tracing and evaluated its effectiveness through morphological analysis. After 3 weeks of taVNS application, the open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety- like behaviors, and the Y- maze test and novel object recognition test (NORT) were used to evaluate recogni-tion memory behaviors, respectively. Results: We found that repetitive taVNS was well tolerated by awake mice, had no effect on anxiety- like behaviors, and significantly improved memory. Conclusion: Our findings suggest that this new taVNS device for repetitive stimula-tion of awake mice is safe, tolerable, and effective.