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

Zakir Mridha, Jan Willem Gee, Yanchen Shi, Rayan Alkashgari, Justin Williams, Aaron Suminski, Matthew P. Ward, Wenhao Zhang and Matthew James McGinley ()
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Zakir Mridha: Baylor College of Medicine
Jan Willem Gee: Baylor College of Medicine
Yanchen Shi: Baylor College of Medicine
Rayan Alkashgari: Department of Biomedical Engineering
Justin Williams: Department of Biomedical Engineering
Aaron Suminski: Department of Biomedical Engineering
Matthew P. Ward: Purdue University
Wenhao Zhang: Baylor College of Medicine
Matthew James McGinley: Baylor College of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Vagus 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.

Date: 2021
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DOI: 10.1038/s41467-021-21730-2

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