Cardiopulmonary Effects of Vagus Nerve Stimulation in Mice.

Abstract

Vagus nerve stimulation (VNS) is an FDA-approved treatment for epilepsy, depression, and chronic stroke. While the effects of VNS are widely studied in rats and large animal models, few studies have characterized VNS in mice due to the practical challenges associated with their small size. However, mouse genetic tools provide a powerful opportunity to elucidate the diverse mechanisms underlying the many effects of VNS. Therefore, to inform the expanding use of mouse models in VNS research, we characterized the cardiopulmonary effects of left versus right VNS in anesthetized C57BL/6 mice. VNS robustly drove decreases in heart rate (HR) and breathing rate (BR) in the majority of mice. VNS-driven changes in BR were not correlated with changes in HR. We found no differences between male and female mice nor in the effects of left versus right VNS. VNS-induced bradycardia was abolished by transection of efferent vagal fibers, consistent with direct descending vagal control of cardiac rhythmicity. In contrast, VNS-driven changes in BR were abolished by both afferent and efferent vagotomies, consistent with the involvement of central feedback circuits in bilaterally coordinated vagal modulation of respiration. These results further our understanding of VNS effects in mice and help inform experimental design and cuff validation protocols for vagal modulation of peripheral versus central circuits in this species.