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bioRxiv · 10.1101/2019.12.28.890111

Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

Mridha, Z.·de Gee, J. W.·Shi, Y.·Alkashgari, R.·Williams, J.·Suminski, A.·Ward, M. P.·Zhang, W.·McGinley, M. J.
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Abstract

AO_SCPLOWBSTRACTC_SCPLOWVagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an optimal zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.

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Mridha, Z., de Gee, J. W., Shi, Y., Alkashgari, R., Williams, J., Suminski, A., Ward, M. P., Zhang, W., McGinley, M. J.. 2019-12-30. Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve. https://doi.org/10.1101/2019.12.28.890111

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