Conveyance of cortical pacing for parkinsonian tremor-like hyperkinetic behavior by subthalamic dysrhythmia
Chen-Syuan Huang,
Guan-Hsun Wang,
Hsiang-Hao Chuang,
Ai-Yu Chuang,
Jui-Yu Yeh,
Yi-Chen Lai,
Ya-Chin Yang
Affiliations
Chen-Syuan Huang
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Guan-Hsun Wang
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Department of Medical Education, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 333, Taiwan
Hsiang-Hao Chuang
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Ai-Yu Chuang
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Jui-Yu Yeh
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Yi-Chen Lai
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Ya-Chin Yang
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 333, Taiwan; Corresponding author
Summary: Parkinson’s disease is characterized by both hypokinetic and hyperkinetic symptoms. While increased subthalamic burst discharges have a direct causal relationship with the hypokinetic manifestations (e.g., rigidity and bradykinesia), the origin of the hyperkinetic symptoms (e.g., resting tremor and propulsive gait) has remained obscure. Neuronal burst discharges are presumed to be autonomous or less responsive to synaptic input, thereby interrupting the information flow. We, however, demonstrate that subthalamic burst discharges are dependent on cortical glutamatergic synaptic input, which is enhanced by A-type K+ channel inhibition. Excessive top-down-triggered subthalamic burst discharges then drive highly correlative activities bottom-up in the motor cortices and skeletal muscles. This leads to hyperkinetic behaviors such as tremors, which are effectively ameliorated by inhibition of cortico-subthalamic AMPAergic synaptic transmission. We conclude that subthalamic burst discharges play an imperative role in cortico-subcortical information relay, and they critically contribute to the pathogenesis of both hypokinetic and hyperkinetic parkinsonian symptoms.
