Frequency Matters: Beta Band Subthalamic Nucleus Deep Brain Stimulation Induces Parkinsonian-like Blink Abnormalities in Normal Rats

摘要

The synchronized beta band oscillations in the basal ganglia-cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta band activity in PD motor symptoms by testing the effects of beta frequency subthalamic nucleus deep brain stimulation (STN DBS) on blink reflex excitability, amplitude, and plasticity in >normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6-OHDA lesions and PD patients. These deficits were not an artifact of STN DBS because when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz DBS exaggerated blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency specific STN DBS can be used to create PD- or dystonic-like symptoms in a normal rat.