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

Z. Mridha, View ORCID ProfileJ. W. de Gee, Y. Shi, R. Alkashgari, J. Williams, A. Suminski, M. P. Ward, W. Zhang, View ORCID ProfileM. J. McGinley
doi: https://doi.org/10.1101/2019.12.28.890111
Z. Mridha
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USAJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, USA
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J. W. de Gee
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USAJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, USA
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  • ORCID record for J. W. de Gee
Y. Shi
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USAJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, USA
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R. Alkashgari
Department of Biomedical Engineering, Madison, WI, USA
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J. Williams
Department of Biomedical Engineering, Madison, WI, USA
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A. Suminski
Department of Biomedical Engineering, Madison, WI, USA
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M. P. Ward
Department of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
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W. Zhang
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USAJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, USA
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M. J. McGinley
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USAJan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, USADepartment of Electrical and Computer Engineering, Rice University, Houston, TX, USA
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  • ORCID record for M. J. McGinley
  • For correspondence: matthew.mcginley@bcm.edu
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Abstract

Vagus nerve stimulation (VNS) is thought to alter the state of the brain by recruiting global neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other brain 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 biosensor for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill, and use it to show that pupil dilation is a biosensor for VNS-evoked cortical neuromodulation. In a ‘goldilocks’ 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 auditory cortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment titratable effects of VNS on brain state.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 30, 2019.
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Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve
Z. Mridha, J. W. de Gee, Y. Shi, R. Alkashgari, J. Williams, A. Suminski, M. P. Ward, W. Zhang, M. J. McGinley
bioRxiv 2019.12.28.890111; doi: https://doi.org/10.1101/2019.12.28.890111
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Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve
Z. Mridha, J. W. de Gee, Y. Shi, R. Alkashgari, J. Williams, A. Suminski, M. P. Ward, W. Zhang, M. J. McGinley
bioRxiv 2019.12.28.890111; doi: https://doi.org/10.1101/2019.12.28.890111

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