title: Axial levodopa-induced dyskinesias and neuronal activity in the dorsal striatum.
abstract: Levodopa-induced dyskinesias are abnormal involuntary movements that limit the effectiveness of treatments for Parkinson's disease. Although dyskinesias involve the striatum, it is unclear how striatal neurons are involved in dyskinetic movements. Here we record from striatal neurons in mice during levodopa-induced axial dyskinesias. We developed an automated 3-dimensional motion tracking system to capture the development of axial dyskinesias at ∼10ms resolution, and correlated these movements with neuronal activity of striatal medium spiny neurons and fast-spiking interneurons. The average firing rate of medium spiny neurons increased as axial dyskinesias developed, and both medium spiny neurons and fast-spiking interneurons were modulated around axial dyskinesias. We also found that delta field potential power increased in the striatum with dyskinesia, and that this increased delta power coupled with striatal neurons. Our findings provide insight into how striatal networks change as levodopa-induced dyskinesias develop, and suggest that increased medium spiny neuron firing, increased delta field potential power, and abnormal delta-coupling may be neurophysiological signatures of dyskinesias. These data could be helpful in understanding the role of the striatum in the pathogenesis of dyskinesias in Parkinson's disease.
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Alberico
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Young-Cho
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Tomas
authors.initials: T
authors.lastname: Lence
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States. Electronic address: Nandakumar-narayanan@uiowa.edu.
authors.forename: Nandakumar S
authors.initials: NS
authors.lastname: Narayanan
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity*; D057205:Automation, Laboratory; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D003700:Delta Rhythm / Q000187:drug effects; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D004567:Electrodes, Implanted; D007839:Functional Laterality; D007980:Levodopa / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010363:Pattern Recognition, Automated
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Parkinson’s disease; fast-spiking interneurons; levodopa-induced dyskinesia; medium spiny neurons; tracking