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dc.contributor.authorYe, Tony
dc.contributor.authorBartlett, Mitchell J
dc.contributor.authorSherman, Scott J
dc.contributor.authorFalk, Torsten
dc.contributor.authorCowen, Stephen L
dc.date.accessioned2021-04-07T22:08:44Z
dc.date.available2021-04-07T22:08:44Z
dc.date.issued2021-03-02
dc.identifier.citationYe, T., Bartlett, M. J., Sherman, S. J., Falk, T., & Cowen, S. L. (2021). Spectral signatures of L-DOPA-induced dyskinesia depend on L-DOPA dose and are suppressed by ketamine. Experimental Neurology, 340, 113670.en_US
dc.identifier.issn0014-4886
dc.identifier.pmid33662379
dc.identifier.doi10.1016/j.expneurol.2021.113670
dc.identifier.urihttp://hdl.handle.net/10150/657644
dc.description.abstractL-DOPA-induced dyskinesias (LID) are debilitating motor symptoms of dopamine-replacement therapy for Parkinson's disease (PD) that emerge after years of L-DOPA treatment. While there is an abundance of research into the cellular and synaptic origins of LID, less is known about how LID impacts systems-level circuits and neural synchrony, how synchrony is affected by the dose and duration of L-DOPA exposure, or how potential novel treatments for LID, such as sub-anesthetic ketamine, alter this activity. Sub-anesthetic ketamine treatments have recently been shown to reduce LID, and ketamine is known to affect neural synchrony. To investigate these questions, we measured movement and local-field potential (LFP) activity from the motor cortex (M1) and the striatum of preclinical rodent models of PD and LID. In the first experiment, we investigated the effect of the LID priming procedures and L-DOPA dose on neural signatures of LID. Two common priming procedures were compared: a high-dose procedure that exposed unilateral 6-hydroxydopamine-lesioned rats to 12 mg/kg L-DOPA for 7 days, and a low-dose procedure that exposed rats to 7 mg/kg L-DOPA for 21 days. Consistent with reports from other groups, 12 mg/kg L-DOPA triggered LID and 80-Hz oscillations; however, these 80-Hz oscillations were not observed after 7 mg/kg administration despite clear evidence of LID, indicating that 80-Hz oscillations are not an exclusive signature of LID. We also found that weeks-long low-dose priming resulted in the emergence of non-oscillatory broadband gamma activity (> 30 Hz) in the striatum and theta-to-high-gamma cross-frequency coupling (CFC) in M1. In a second set of experiments, we investigated how ketamine exposure affects spectral signatures of low-dose L-DOPA priming. During each neural recording session, ketamine was delivered through 5 injections (20 mg/kg, i.p.) administered every 2 h. We found that ketamine exposure suppressed striatal broadband gamma associated with LID but enhanced M1 broadband activity. We also found that M1 theta-to-high-gamma CFC associated with the LID on-state was suppressed by ketamine. These results suggest that ketamine's therapeutic effects are region specific. Our findings also have clinical implications, as we are the first to report novel oscillatory signatures of the common low-dose LID priming procedure that more closely models dopamine replacement therapy in individuals with PD. We also identify neural correlates of the anti-dyskinetic activity of sub-anesthetic ketamine treatment.en_US
dc.language.isoenen_US
dc.publisherAcademic Press Inc.en_US
dc.rightsCopyright © 2021. Published by Elsevier Inc.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en_US
dc.subjectcross-frequency couplingen_US
dc.subjectgammaen_US
dc.subjecthigh-frequency oscillationen_US
dc.subjectketamineen_US
dc.subjectlevodopa-induced dyskinesiaen_US
dc.subjectOscillationen_US
dc.subjectParkinson's diseaseen_US
dc.titleSpectral signatures of L-DOPA-induced dyskinesia depend on L-DOPA dose and are suppressed by ketamineen_US
dc.typeArticleen_US
dc.identifier.eissn1090-2430
dc.contributor.departmentDepartment of Neurology, University of Arizona College of Medicineen_US
dc.contributor.departmentDepartment of Pharmacology, University of Arizona College of Medicineen_US
dc.contributor.departmentDepartment of Psychology, University of Arizona College of Medicineen_US
dc.identifier.journalExperimental Neurologyen_US
dc.description.note12 month embargo; first published online 2 March 2021en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleExperimental neurology
dc.source.volume340
dc.source.beginpage113670
dc.source.endpage
dc.source.countryUnited States


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