Norepinephrine and Serotonin are Required for Vagus Nerve Stimulation Directed Cortical Plasticity

dc.contributor.ORCID0000-0003-4225-241X (Hays, SA)
dc.contributor.VIAF13146094343400332984 (Hays, SA)
dc.contributor.authorHulsey, Daniel R.
dc.contributor.authorShedd, Cristine M.
dc.contributor.authorSarker, Sadmaan F.
dc.contributor.authorKilgard, Michael P.
dc.contributor.authorHays, Seth A.
dc.contributor.utdAuthorHulsey, Daniel R.
dc.contributor.utdAuthorShedd, Cristine M.
dc.contributor.utdAuthorSarker, Sadmaan F.
dc.contributor.utdAuthorKilgard, Michael P.
dc.contributor.utdAuthorHays, Seth A.
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dc.description.abstractVagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. This effect is hypothesized to be mediated by VNS-dependent engagement of neuromodulatory networks. VNS influences activity in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), but the involvement of these neuromodulatory networks in VNS-directed plasticity is unknown. We tested the hypothesis that cortical norepinephrine and serotonin are required for VNS-dependent enhancement of motor cortex plasticity. Rats were trained on a lever pressing task emphasizing proximal forelimb use. Once proficient, all rats received a surgically implanted vagus nerve cuff and cortical injections of either immunotoxins to deplete serotonin or norepinephrine, or vehicle control. Following surgical recovery, rats received half second bursts of 0.8 mA or sham VNS after successful trials. After five days of pairing intracortical microstimulation (ICMS) was performed in the motor cortex contralateral to the trained limb. VNS paired with training more than doubled cortical representations of proximal forelimb movements. Depletion of either cortical norepinephrine or serotonin prevented this effect. The requirement of multiple neuromodulators is consistent with earlier studies showing that these neuromodulators regulate synaptic plasticity in a complimentary fashion. ©2019 Elsevier Inc.
dc.description.departmentErik Jonsson School of Engineering and Computer Science
dc.description.departmentSchool of Behavioral and Brain Sciences
dc.description.departmentTexas Biomedical Device Center
dc.description.sponsorshipNational Institutes of Health R01NS094384, R01NS085167, R01NS103803; Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO) Electrical Prescriptions (ElectRx) program under the auspices of Dr. Eric Van Gieson through the Naval Information Warfare Center, Pacific Cooperative Agreement No. N66001-15-2-4057; Naval Information Warfare Center, Pacific Grant/Contract No. N66001-17-2-4011
dc.identifier.bibliographicCitationHulsey, D. R., C. M. Shedd, S. F. Sarker, M. P. Kilgard, et al. 2019. "Norepinephrine and serotonin are required for vagus nerve stimulation directed cortical plasticity." Experimental Neurology 320: art. 112975, doi: 10.1016/j.expneurol.2019.112975
dc.publisherAcademic Press Inc.
dc.rights©2019 Elsevier Inc.
dc.source.journalExperimental Neurology
dc.subjectMotor cortex
dc.subject.meshVagus Nerve Stimulation
dc.titleNorepinephrine and Serotonin are Required for Vagus Nerve Stimulation Directed Cortical Plasticity