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
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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