Pairing vagus nerve stimulation with tones drives plasticity across the auditory pathway.

Previous studies have demonstrated that pairing vagus nerve stimulation (VNS) with sounds can enhance the primary auditory cortex (A1) response to the paired sound. The neural response to sounds following VNS-sound pairing in other subcortical and cortical auditory fields has not been documented. We predicted that VNS-tone pairing would increase neural responses to the paired tone frequency across the auditory pathway. In this study, we paired VNS with the presentation of a 9-kHz tone 300 times a day for 20 days. We recorded neural responses to tones from 2,950 sites in the inferior colliculus (IC), A1, anterior auditory field (AAF), and posterior auditory field (PAF) 24 h after the last pairing session in anesthetized rats. We found that VNS-tone pairing increased the percentage of IC, A1, AAF, and PAF that responds to the paired tone frequency. Across all tested auditory fields, the response strength to tones was strengthened in VNS-tone paired rats compared with control rats. VNS-tone pairing reduced spontaneous activity, frequency selectivity, and response threshold across the auditory pathway. This is the first study to document both cortical and subcortical plasticity following VNS-sound pairing. Our findings suggest that VNS paired with sound presentation is an effective method to enhance auditory processing. Previous studies have reported primary auditory cortex plasticity following vagus nerve stimulation (VNS) paired with a sound. This study extends previous findings by documenting that fields across the auditory pathway are altered by VNS-tone pairing. VNS-tone pairing increases the percentage of each field that responds to the paired tone frequency. This is the first study to document both cortical and subcortical plasticity following VNS-sound pairing.