Conveyance of cortical pacing for parkinsonian tremor-like hyperkinetic behavior by subthalamic dysrhythmia
Autor: | Jui-Yu Yeh, Yi-Chen Lai, Hsiang-Hao Chuang, Chen-Syuan Huang, Guan-Hsun Wang, Ya-Chin Yang, Ai-Yu Chuang |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male burst discharge QH301-705.5 Glutamic Acid Propulsive gait Neurotransmission Hyperkinesis Globus Pallidus Synaptic Transmission General Biochemistry Genetics and Molecular Biology Membrane Potentials 03 medical and health sciences Glutamatergic Parkinsonian Symptoms 0302 clinical medicine Subthalamic Nucleus Tremor Excitatory Amino Acid Agonists Medicine Animals Humans Resting tremor Biology (General) 4-Aminopyridine Parkinson Disease Secondary Rats Wistar Muscle Skeletal alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid 6-Cyano-7-nitroquinoxaline-2 3-dione brain oscillation business.industry Motor Cortex Motor control cortico-subcortical reentrant loop cortico-subthalamic transmission medicine.disease Rats Mice Inbred C57BL Optogenetics 030104 developmental biology basal ganglia network Synapses Female business A-type K+ channel Neuroscience Excitatory Amino Acid Antagonists 030217 neurology & neurosurgery |
Zdroj: | Cell Reports, Vol 35, Iss 3, Pp 109007-(2021) |
ISSN: | 2211-1247 |
Popis: | 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. |
Databáze: | OpenAIRE |
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