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 language | English |
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Article number | 109007 |
Journal | Cell Reports |
Volume | 35 |
Issue number | 3 |
DOIs | |
State | Published - 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