Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications
Abstract Background Vagus nerve stimulation (VNS) is a FDA approved therapy regularly used to treat a variety of neurological disorders that impact the central nervous system (CNS) including epilepsy and stroke. Putatively, the therapeutic efficacy of VNS results from its action on neuromodulatory c...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Bioelectronic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s42234-023-00111-8 |
| _version_ | 1797836346778189824 |
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| author | Aaron J. Suminski Abigail Z. Rajala Rasmus M. Birn Ellie M. Mueller Margaret E. Malone Jared P. Ness Caitlyn Filla Kevin Brunner Alan B. McMillan Samuel O. Poore Justin C. Williams Dhanabalan Murali Andrea Brzeczkowski Samuel A. Hurley Aaron M. Dingle Weifeng Zeng Wendell B. Lake Kip A. Ludwig Luis C. Populin |
| author_facet | Aaron J. Suminski Abigail Z. Rajala Rasmus M. Birn Ellie M. Mueller Margaret E. Malone Jared P. Ness Caitlyn Filla Kevin Brunner Alan B. McMillan Samuel O. Poore Justin C. Williams Dhanabalan Murali Andrea Brzeczkowski Samuel A. Hurley Aaron M. Dingle Weifeng Zeng Wendell B. Lake Kip A. Ludwig Luis C. Populin |
| author_sort | Aaron J. Suminski |
| collection | DOAJ |
| description | Abstract Background Vagus nerve stimulation (VNS) is a FDA approved therapy regularly used to treat a variety of neurological disorders that impact the central nervous system (CNS) including epilepsy and stroke. Putatively, the therapeutic efficacy of VNS results from its action on neuromodulatory centers via projections of the vagus nerve to the solitary tract nucleus. Currently, there is not an established large animal model that facilitates detailed mechanistic studies exploring how VNS impacts the function of the CNS, especially during complex behaviors requiring motor action and decision making. Methods We describe the anatomical organization, surgical methodology to implant VNS electrodes on the left gagus nerve and characterization of target engagement/neural interface properties in a non-human primate (NHP) model of VNS that permits chronic stimulation over long periods of time. Furthermore, we describe the results of pilot experiments in a small number of NHPs to demonstrate how this preparation might be used in an animal model capable of performing complex motor and decision making tasks. Results VNS electrode impedance remained constant over months suggesting a stable interface. VNS elicited robust activation of the vagus nerve which resulted in decreases of respiration rate and/or partial pressure of carbon dioxide in expired air, but not changes in heart rate in both awake and anesthetized NHPs. Conclusions We anticipate that this preparation will be very useful to study the mechanisms underlying the effects of VNS for the treatment of conditions such as epilepsy and depression, for which VNS is extensively used, as well as for the study of the neurobiological basis underlying higher order functions such as learning and memory. |
| first_indexed | 2024-04-09T15:07:19Z |
| format | Article |
| id | doaj.art-53a446a8268a482fab5f2701a44dc9a7 |
| institution | Directory Open Access Journal |
| issn | 2332-8886 |
| language | English |
| last_indexed | 2024-04-09T15:07:19Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Bioelectronic Medicine |
| spelling | doaj.art-53a446a8268a482fab5f2701a44dc9a72023-04-30T11:22:39ZengBMCBioelectronic Medicine2332-88862023-04-019111710.1186/s42234-023-00111-8Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applicationsAaron J. Suminski0Abigail Z. Rajala1Rasmus M. Birn2Ellie M. Mueller3Margaret E. Malone4Jared P. Ness5Caitlyn Filla6Kevin Brunner7Alan B. McMillan8Samuel O. Poore9Justin C. Williams10Dhanabalan Murali11Andrea Brzeczkowski12Samuel A. Hurley13Aaron M. Dingle14Weifeng Zeng15Wendell B. Lake16Kip A. Ludwig17Luis C. Populin18Department of Neurological Surgery, University of Wisconsin-MadisonDepartment of Neuroscience, University of Wisconsin-MadisonDepartment of Psychiatry, University of Wisconsin-MadisonDepartment of Neuroscience, University of Wisconsin-MadisonDepartment of Neuroscience, University of Wisconsin-MadisonWisconsin Institute for Translational Neuroengineering, University of Wisconsin-MadisonDepartment of Neuroscience, University of Wisconsin-MadisonWisconsin National Primate Research Center, University of Wisconsin-MadisonDepartment of Radiology, University of Wisconsin-MadisonDivision of Plastic Surgery, University of Wisconsin-MadisonDepartment of Neurological Surgery, University of Wisconsin-MadisonDepartment of Medical Physics, University of Wisconsin-MadisonDepartment of Neurological Surgery, University of Wisconsin-MadisonDepartment of Radiology, University of Wisconsin-MadisonDivision of Plastic Surgery, University of Wisconsin-MadisonDivision of Plastic Surgery, University of Wisconsin-MadisonDepartment of Neurological Surgery, University of Wisconsin-MadisonDepartment of Neurological Surgery, University of Wisconsin-MadisonDepartment of Neuroscience, University of Wisconsin-MadisonAbstract Background Vagus nerve stimulation (VNS) is a FDA approved therapy regularly used to treat a variety of neurological disorders that impact the central nervous system (CNS) including epilepsy and stroke. Putatively, the therapeutic efficacy of VNS results from its action on neuromodulatory centers via projections of the vagus nerve to the solitary tract nucleus. Currently, there is not an established large animal model that facilitates detailed mechanistic studies exploring how VNS impacts the function of the CNS, especially during complex behaviors requiring motor action and decision making. Methods We describe the anatomical organization, surgical methodology to implant VNS electrodes on the left gagus nerve and characterization of target engagement/neural interface properties in a non-human primate (NHP) model of VNS that permits chronic stimulation over long periods of time. Furthermore, we describe the results of pilot experiments in a small number of NHPs to demonstrate how this preparation might be used in an animal model capable of performing complex motor and decision making tasks. Results VNS electrode impedance remained constant over months suggesting a stable interface. VNS elicited robust activation of the vagus nerve which resulted in decreases of respiration rate and/or partial pressure of carbon dioxide in expired air, but not changes in heart rate in both awake and anesthetized NHPs. Conclusions We anticipate that this preparation will be very useful to study the mechanisms underlying the effects of VNS for the treatment of conditions such as epilepsy and depression, for which VNS is extensively used, as well as for the study of the neurobiological basis underlying higher order functions such as learning and memory.https://doi.org/10.1186/s42234-023-00111-8Vagus nerve stimulationfMRIPETHistology |
| spellingShingle | Aaron J. Suminski Abigail Z. Rajala Rasmus M. Birn Ellie M. Mueller Margaret E. Malone Jared P. Ness Caitlyn Filla Kevin Brunner Alan B. McMillan Samuel O. Poore Justin C. Williams Dhanabalan Murali Andrea Brzeczkowski Samuel A. Hurley Aaron M. Dingle Weifeng Zeng Wendell B. Lake Kip A. Ludwig Luis C. Populin Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications Bioelectronic Medicine Vagus nerve stimulation fMRI PET Histology |
| title | Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications |
| title_full | Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications |
| title_fullStr | Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications |
| title_full_unstemmed | Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications |
| title_short | Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications |
| title_sort | vagus nerve stimulation in the non human primate implantation methodology characterization of nerve anatomy target engagement and experimental applications |
| topic | Vagus nerve stimulation fMRI PET Histology |
| url | https://doi.org/10.1186/s42234-023-00111-8 |
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