PT  - JOURNAL ARTICLE
AU  - Kathleen A. Martin
AU  - Eleni S. Papadoyannis
AU  - Jennifer K. Schiavo
AU  - Saba Shokat Fadaei
AU  - Nesibe Z. Temiz
AU  - Matthew J. McGinley
AU  - David A. McCormick
AU  - Robert C. Froemke
TI  - Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning
AID  - 10.1101/2022.01.28.478197
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.28.478197
4099  - http://biorxiv.org/content/early/2022/01/28/2022.01.28.478197.short
4100  - http://biorxiv.org/content/early/2022/01/28/2022.01.28.478197.full
AB  - Perception can be refined by experience up to certain limits. It is unclear if limitations are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies highlight the utility of peripheral nerve stimulation - specifically vagus nerve stimulation (VNS) - for altering neural activity and augmenting experience-dependent plasticity, although little is known about central mechanisms recruited by VNS. Here we developed an auditory discrimination task for mice implanted with a VNS electrode. VNS occurring during behavior gradually improved discrimination abilities beyond the level achieved by training alone. Using two-photon imaging, we identified changes to auditory cortical responses and activation of cortically-projecting cholinergic axons with VNS. Anatomical and optogenetic experiments revealed that VNS seemed to enhance task performance via activation of the central cholinergic system. These results highlight the importance of cholinergic modulation for the efficacy of VNS, perhaps enabling further refinement of VNS methodology for clinical conditions.Competing Interest StatementThe authors have declared no competing interest.