Dyskinesia is Closely Associated with Synchronization of Theta Oscillatory Activity Between the Substantia Nigra Pars Reticulata and Motor Cortex in the Off L-dopa State in Rats
Jiazhi Chen1 • Qiang Wang1,3 • Nanxiang Li1 • Shujie Huang1 • Min Li1 • Junbin Cai1 • Yuzheng Wang2 • Huantao Wen1 • Siyuan Lv1 • Ning Wang2 • Jinyan Wang2 • Fei Luo2 • Wangming Zhang1
1 The National Key Clinic Specialty, The Engineering Technology Research Center of the Ministry of Education of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
2 Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
3 Movement Disorders and Neuromodulation Unit, Department for Neurology, Charite´ - University Medicine Berlin, 10117 Berlin, Germany
Abstract
Excessive theta (θ) frequency oscillation and synchronization in the basal ganglia (BG) has been reported in elderly parkinsonian patients and animal models of levodopa (L-dopa)-induced dyskinesia (LID), particularly the θ oscillation recorded during periods when L-dopa is withdrawn (the off L-dopa state). To gain insight into processes underlying this activity, we explored the relationship between primary motor cortex (M1) oscillatory activity and BG output in LID. We recorded local field potentials in the substantia nigra pars reticulata (SNr) and M1 of awake, inattentive resting rats before and after L-dopa priming in Sham control, Parkinson disease model, and LID model groups. We found that chronic L-dopa increased θ synchronization and information flow between the SNr and M1 in off L-dopa state LID rats, with a SNr-to-M1 flow directionality. Compared with the on state, θ oscillational activity (θ synchronization and information flow) during the off state were more closely associated with abnormal involuntary movements. Our findings indicate that θ oscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1 θ oscillation may participate in the induction of dyskinesia.
Keywords
Parkinson’s disease; Dyskinesia; Substantia nigra pars reticulata; Primary motor cortex; Synchronization