{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:31:25Z","timestamp":1788262285613,"version":"build-2803163510"},"reference-count":42,"publisher":"IMR Press","issue":"12","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"framework of State assignment","award":["075-00224-24-03"],"award-info":[{"award-number":["075-00224-24-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Background: Long-term use of levodopa, a metabolic precursor of dopamine (DA) for alleviation of motor symptoms in Parkinson\u2019s disease (PD), can cause a serious side effect known as levodopa-induced dyskinesia (LID). With the development of LID, high-frequency gamma oscillations (~100 Hz) are registered in the motor cortex (MCx) in patients with PD and rats with experimental PD. Studying alterations in the activity within major components of motor networks during transition from levodopa-off state to dyskinesia can provide useful information about their contribution to the development of abnormal gamma oscillations and LID. Methods: Freely moving rats with unilateral 6-hydroxydopamine hydrobromide (6-OHDA)-induced nigral DA cell lesions were administered a high dose of levodopa for 7 days. Local field potentials (LFPs) and neuronal activity were recorded from electrodes implanted in the motor cortex (MCx), ventromedial nucleus of the thalamus (VM), and substantia nigra pars reticulata nucleus (SNpr). Results: Levodopa reduced the power of beta oscillations (30\u201336 Hz) associated with bradykinesia in PD rats in three divisions of the motor neural network (MCx, VM, and SNpr) and prompted subsequent emergence of robust high-frequency gamma oscillations (80\u2013120 Hz) in VM and MCx, but not SNpr, LFPs. Gamma oscillations were strongly associated with the occurrence of abnormal involuntary movements (AIMs) and accompanied by an increase in spiking rates in the VM and MCx and enlarged spike-LFP synchronization with cortical gamma oscillations (68% in the VM and 34% in the MCx). In contrast, SNpr LFPs did not exhibit gamma oscillations during LID, and neuronal activity in most recordings (87%) was largely decreased and not synchronized with VM or MCx LFPs. Administration of the antidyskinetic drug 8-hydroxy-2-(dipropylamino)-tetraline hydrobromide (8-OH-DPAT) restored the initial characteristics of LFPs (30\u201336 Hz oscillations), rates of neuronal activity, and bradykinesia. Inhibition of VM neurons by the gamma-aminobutyric acid (GABA-A)-agonist muscimol during LID eliminated high gamma oscillations in the MCx and VM, but not dyskinesia, suggesting that gamma oscillations are not critical for the expression of AIMs. In contrast, chemogenetic activation of SNpr neurons during LID eliminated both gamma oscillations and dyskinesia. Conclusions: These findings suggest that levodopa treatment leads to crucial reduction of inhibitory control over motor networks due to a large decline in spiking of most SNpr GABAergic projecting neurons, which causes persistent hyperactivity in motor circuits, leading to the appearance of thalamocortical gamma oscillations and LID.<\/jats:p>","DOI":"10.31083\/j.jin2312221","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T11:05:21Z","timestamp":1735556721000},"source":"Crossref","is-referenced-by-count":6,"title":["Coherent Changes in Neural Motor Network Activity during Levodopa-Induced Dyskinesia in a Rat Model of Parkinson\u2019s Disease"],"prefix":"10.31083","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5760-051X","authenticated-orcid":true,"given":"Elena S.","family":"Brazhnik","sequence":"first","affiliation":[{"name":"Federal State Budgetary Educational Institution, Institute of Theoretical and Experimental Biophysics, 142290 Pushchino, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-127X","authenticated-orcid":true,"given":"Ivan E.","family":"Mysin","sequence":"first","affiliation":[{"name":"Federal State Budgetary Educational Institution, Institute of Theoretical and Experimental Biophysics, 142290 Pushchino, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1501-9508","authenticated-orcid":true,"given":"Lyudmila B.","family":"Popova","sequence":"first","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-4566","authenticated-orcid":true,"given":"Vladislav V.","family":"Minaychev","sequence":"first","affiliation":[{"name":"Federal State Budgetary Educational Institution, Institute of Theoretical and Experimental Biophysics, 142290 Pushchino, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9192-5037","authenticated-orcid":true,"given":"Nikolay I.","family":"Novikov","sequence":"first","affiliation":[{"name":"Federal State Budgetary Educational Institution, Institute of Theoretical and Experimental Biophysics, 142290 Pushchino, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Jenkinson N, K\u00fchn AA, Brown P. \u03b3 oscillations in the human basal ganglia. Experimental Neurology. 2013; 245: 72\u201376.","DOI":"10.1016\/j.expneurol.2012.07.005"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Brittain JS, Brown P. Oscillations and the basal ganglia: motor control and beyond. NeuroImage. 2014; 85 Pt 2: 637\u2013647.","DOI":"10.1016\/j.neuroimage.2013.05.084"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Swann NC, de Hemptinne C, Miocinovic S, Qasim S, Wang SS, Ziman N, et al. Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson\u2019s Disease. The Journal of Neuroscience. 2016; 36: 6445\u20136458.","DOI":"10.1523\/JNEUROSCI.1128-16.2016"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"di Biase L, Pecoraro PM, Carbone SP, Caminiti ML, Di Lazzaro V. Levodopa-Induced Dyskinesias in Parkinson\u2019s Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions. Journal of Clinical Medicine. 2023; 12: 4427.","DOI":"10.3390\/jcm12134427"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Halje P, Tamt\u00e8 M, Richter U, Mohammed M, Cenci MA, Petersson P. Levodopa-induced dyskinesia is strongly associated with resonant cortical oscillations. The Journal of Neuroscience. 2012; 32: 16541\u201316551.","DOI":"10.1523\/JNEUROSCI.3047-12.2012"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Delaville C, McCoy AJ, Gerber CM, Cruz AV, Walters JR. Subthalamic nucleus activity in the awake hemiparkinsonian rat: relationships with motor and cognitive networks. The Journal of Neuroscience. 2015; 35: 6918\u20136930.","DOI":"10.1523\/JNEUROSCI.0587-15.2015"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Dupre KB, Cruz AV, McCoy AJ, Delaville C, Gerber CM, Eyring KW, et al. Effects of L-dopa priming on cortical high beta and high gamma oscillatory activity in a rodent model of Parkinson\u2019s disease. Neurobiology of Disease. 2016; 86: 1\u201315.","DOI":"10.1016\/j.nbd.2015.11.009"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Petersson P, Halje P, Cenci MA. Significance and Translational Value of High-Frequency Cortico-Basal Ganglia Oscillations in Parkinson\u2019s Disease. Journal of Parkinson\u2019s Disease. 2019; 9: 183\u2013196.","DOI":"10.3233\/JPD-181480"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"G\u00fcttler C, Altsch\u00fcler J, Tanev K, B\u00f6ckmann S, Haumesser JK, Nikulin VV, et al. Levodopa-Induced Dyskinesia Are Mediated by Cortical Gamma Oscillations in Experimental Parkinsonism. Movement Disorders. 2021; 36: 927\u2013937.","DOI":"10.1002\/mds.28403"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Kempf F, Br\u00fccke C, Salih F, Trottenberg T, Kupsch A, Schneider GH, et al. Gamma activity and reactivity in human thalamic local field potentials. The European Journal of Neuroscience. 2009; 29: 943\u2013953.","DOI":"10.1111\/j.1460-9568.2009.06655.x"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Brazhnik E, McCoy AJ, Novikov N, Hatch CE, Walters JR. Ventral Medial Thalamic Nucleus Promotes Synchronization of Increased High Beta Oscillatory Activity in the Basal Ganglia-Thalamocortical Network of the Hemiparkinsonian Rat. The Journal of Neuroscience. 2016; 36: 4196\u20134208.","DOI":"10.1523\/JNEUROSCI.3582-15.2016"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Nakamura KC, Sharott A, Tanaka T, Magill PJ. Input Zone-Selective Dysrhythmia in Motor Thalamus after Dopamine Depletion. The Journal of Neuroscience. 2021; 41: 10382\u201310404.","DOI":"10.1523\/JNEUROSCI.1753-21.2021"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Cavarretta F, Jaeger D. Modeling Synaptic Integration of Bursty and \u03b2 Oscillatory Inputs in Ventromedial Motor Thalamic Neurons in Normal and Parkinsonian States. eNeuro. 2023; 10: ENEURO.0237\u201323.2023.","DOI":"10.1523\/ENEURO.0237-23.2023"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Avila I, Parr-Brownlie LC, Brazhnik E, Casta\u00f1eda E, Bergstrom DA, Walters JR. Beta frequency synchronization in basal ganglia output during rest and walk in a hemiparkinsonian rat. Experimental Neurology. 2010; 221: 307\u2013319.","DOI":"10.1016\/j.expneurol.2009.11.016"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Fabbrini A, Guerra A. Pathophysiological Mechanisms and Experimental Pharmacotherapy for L-Dopa-Induced Dyskinesia. Journal of Experimental Pharmacology. 2021; 13: 469\u2013485.","DOI":"10.2147\/JEP.S265282"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Brazhnik E, Novikov N, McCoy AJ, Ilieva NM, Ghraib MW, Walters JR. Early decreases in cortical mid-gamma peaks coincide with the onset of motor deficits and precede exaggerated beta build-up in rat models for Parkinson\u2019s disease. Neurobiology of Disease. 2021; 155: 105393.","DOI":"10.1016\/j.nbd.2021.105393"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Lundblad M, Andersson M, Winkler C, Kirik D, Wierup N, Cenci MA. Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson\u2019s disease. The European Journal of Neuroscience. 2002; 15: 120\u2013132.","DOI":"10.1046\/j.0953-816x.2001.01843.x"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Torrence C, Compo GP. A Practical Guide to Wavelet Analysis. Bulletin of the American Meteorological Society. 1998; 79: 61\u201378. <$0061:APGTWA$>$2.0.CO;2","DOI":"10.1175\/1520-0477(1998)079$"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Brazhnik E, Cruz AV, Avila I, Wahba MI, Novikov N, Ilieva NM, et al. State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats. The Journal of Neuroscience. 2012; 32: 7869\u20137880.","DOI":"10.1523\/JNEUROSCI.0943-12.2012"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Altwal F, Padovan-Neto FE, Ritger A, Steiner H, West AR. Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson\u2019s Disease. Molecules. 2021; 26: 5790.","DOI":"10.3390\/molecules26195790"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Pinna A, Ko WKD, Costa G, Tronci E, Fidalgo C, Simola N, et al. Antidyskinetic effect of A2A and 5HT1A\/1B receptor ligands in two animal models of Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2016; 31: 501\u2013511.","DOI":"10.1002\/mds.26475"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Bi Y, Wang P, Yu J, Wang Z, Yang H, Deng Y, et al. Eltoprazine modulated gamma oscillations on ameliorating L-dopa-induced dyskinesia in rats. CNS Neuroscience & Therapeutics. 2023; 29: 2998\u20133013.","DOI":"10.1111\/cns.14241"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Skovg\u00e5rd K, Barrientos SA, Petersson P, Halje P, Cenci MA. Distinctive Effects of D1 and D2 Receptor Agonists on Cortico-Basal Ganglia Oscillations in a Rodent Model of L-DOPA-Induced Dyskinesia. Neurotherapeutics. 2023; 20: 304\u2013324.","DOI":"10.1007\/s13311-022-01309-5"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Cenci MA, Kumar A. Cells, pathways, and models in dyskinesia research. Current Opinion in Neurobiology. 2024; 84: 102833.","DOI":"10.1016\/j.conb.2023.102833"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Litvak V, Eusebio A, Jha A, Oostenveld R, Barnes G, Foltynie T, et al. Movement-related changes in local and long-range synchronization in Parkinson\u2019s disease revealed by simultaneous magnetoencephalography and intracranial recordings. The Journal of Neuroscience. 2012; 32: 10541\u201310553.","DOI":"10.1523\/JNEUROSCI.0767-12.2012"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Alegre M, Alonso-Frech F, Rodr\u00edguez-Oroz MC, Guridi J, Zamarbide I, Valencia M, et al. Movement-related changes in oscillatory activity in the human subthalamic nucleus: ipsilateral vs. contralateral movements. The European Journal of Neuroscience. 2005; 22: 2315\u20132324.","DOI":"10.1111\/j.1460-9568.2005.04409.x"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Trottenberg T, Fogelson N, K\u00fchn AA, Kivi A, Kupsch A, Schneider GH, et al. Subthalamic gamma activity in patients with Parkinson\u2019s disease. Experimental Neurology. 2006; 200: 56\u201365.","DOI":"10.1016\/j.expneurol.2006.01.012"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Alegre M, L\u00f3pez-Azc\u00e1rate J, Alonso-Frech F, Rodr\u00edguez-Oroz MC, Valencia M, Guridi J, et al. Subthalamic activity during diphasic dyskinesias in Parkinson\u2019s disease. Movement Disorders. 2012; 27: 1178\u20131181.","DOI":"10.1002\/mds.25090"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Ozturk M, Kaku H, Jimenez-Shahed J, Viswanathan A, Sheth SA, Kumar S, et al. Subthalamic Single Cell and Oscillatory Neural Dynamics of a Dyskinetic Medicated Patient With Parkinson\u2019s Disease. Frontiers in Neuroscience. 2020; 14: 391.","DOI":"10.3389\/fnins.2020.00391"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Wiest C, Torrecillos F, Tinkhauser G, Pogosyan A, Morgante F, Pereira EA, et al. Finely-tuned gamma oscillations: Spectral characteristics and links to dyskinesia. Experimental Neurology. 2022; 351: 113999.","DOI":"10.1016\/j.expneurol.2022.113999"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Meidahl AC, Moll CKE, van Wijk BCM, Gulberti A, Tinkhauser G, Westphal M, et al. Synchronised spiking activity underlies phase amplitude coupling in the subthalamic nucleus of Parkinson\u2019s disease patients. Neurobiology of Disease. 2019; 127: 101\u2013113.","DOI":"10.1016\/j.nbd.2019.02.005"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Li M, Wang X, Yao X, Wang X, Chen F, Zhang X, et al. Roles of Motor Cortex Neuron Classes in Reach-Related Modulation for Hemiparkinsonian Rats. Frontiers in Neuroscience. 2021; 15: 645849.","DOI":"10.3389\/fnins.2021.645849"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Sun S, Wang X, Shi X, Fang H, Sun Y, Li M, et al. Neural pathway connectivity and discharge changes between M1 and STN in hemiparkinsonian rats. Brain Research Bulletin. 2023; 196: 1\u201319.","DOI":"10.1016\/j.brainresbull.2023.03.002"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Stark E, Levi A, Rotstein HG. Network resonance can be generated independently at distinct levels of neuronal organization. PLoS Computational Biology. 2022; 18: e1010364.","DOI":"10.1371\/journal.pcbi.1010364"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Pena RFO, Rotstein HG. The voltage and spiking responses of subthreshold resonant neurons to structured and fluctuating inputs: persistence and loss of resonance and variability. Biological Cybernetics. 2022; 116: 163\u2013190.","DOI":"10.1007\/s00422-021-00919-0"},{"key":"ref36","unstructured":"Brazhnik ES, Novikov NI, Dupre KB, Wahba MI, McCoy A, Walters JR. Dissociation of high frequency (100 Hz) oscillatory activity within the thalamocortical network from L-DOPA-induced dyskinesia in hemiparkinsonian rats. SfN Abstract, 2013 on-line"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Picazio S, Ponzo V, Caltagirone C, Brusa L, Koch G. Dysfunctional inhibitory control in Parkinson\u2019s disease patients with levodopa-induced dyskinesias. Journal of Neurology. 2018; 265: 2088\u20132096.","DOI":"10.1007\/s00415-018-8945-1"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Si Q, Gan C, Zhang H, Cao X, Sun H, Wang M, et al. Altered dynamic functional network connectivity in levodopa-induced dyskinesia of Parkinson\u2019s disease. CNS Neuroscience & Therapeutics. 2023; 29: 192\u2013201.","DOI":"10.1111\/cns.13994"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Mirabella G, Pilotto A, Rizzardi A, Montalti M, Olivola E, Zatti C, et al. Effects of dopaminergic treatment on inhibitory control differ across Hoehn and Yahr stages of Parkinson\u2019s disease. Brain Communications. 2023; 6: fcad350.","DOI":"10.1093\/braincomms\/fcad350"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Luo L, Callaway EM, Svoboda K. Genetic Dissection of Neural Circuits: A Decade of Progress. Neuron. 2018; 98: 256\u2013281.","DOI":"10.1016\/j.neuron.2018.03.040"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Smith Y, Galvan A, Ellender TJ, Doig N, Villalba RM, Huerta-Ocampo I, et al. The thalamostriatal system in normal and diseased states. Frontiers in Systems Neuroscience. 2014; 8: 5.","DOI":"10.3389\/fnsys.2014.00005"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Bonomo R, Elia AE, Bonomo G, Romito LM, Mariotti C, Devigili G, et al. Deep brain stimulation in Huntington\u2019s disease: a literature review. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2021; 42: 4447\u20134457.","DOI":"10.1007\/s10072-021-05527-1"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/23\/12\/10.31083\/j.jin2312221","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T11:13:55Z","timestamp":1735557235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/23\/12\/10.31083\/j.jin2312221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,24]]},"references-count":42,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024]]}},"alternative-id":["S0219-6352(24)00864-7"],"URL":"https:\/\/doi.org\/10.31083\/j.jin2312221","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,24]]},"article-number":"221"}}