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*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Article number109007
JournalCell Reports
Volume35
Issue number3
DOIs
StatePublished - 20 04 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors

Keywords

  • A-type K channel
  • basal ganglia network
  • brain oscillation
  • burst discharge
  • cortico-subcortical reentrant loop
  • cortico-subthalamic transmission
  • glutamatergic transmission
  • hyperdirect pathway
  • motor control
  • parkinsonian tremor

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