Effects of L-dopa priming on cortical high beta and high gamma oscillatory activity in a rodent model of Parkinson's disease.

ABSTRACT

Prolonged L-dopa treatment in Parkinson's disease (PD) often leads to the expression of abnormal involuntary movements known as L-dopa-induced dyskinesia. Recently, dramatic 80 Hz oscillatory local field potential (LFP) activity within the primary motor cortex has been linked to dyskinetic symptoms in a rodent model of PD and attributed to stimulation of cortical dopamine D1 receptors. To characterize the relationship between high gamma (70-110 Hz) cortical activity and the development of L-dopa-induced dyskinesia, cortical LFP and spike signals were recorded in hemiparkinsonian rats treated with L-dopa for 7 days, and dyskinesia was quantified using the abnormal involuntary movements (AIMs) scale. The relationship between high gamma and dyskinesia was further probed by assessment of the effects of pharmacological agents known to induce or modulate dyskinesia expression. Findings demonstrate that AIMs and high gamma LFP power increase between days 1 and 7 of L-dopa priming. Notably, high beta (25-35 Hz) power associated with parkinsonian bradykinesia decreased as AIMs and high gamma LFP power increased during priming. After priming, rats were treated with the D1 agonist SKF81297 and the D2 agonist quinpirole. Both dopamine agonists independently induced AIMs and high gamma cortical activity that were similar to that induced by L-dopa, showing that this LFP activity is neither D1 nor D2 receptor specific. The serotonin 1A receptor agonist 8-OH-DPAT reduced L-dopa- and DA agonist-induced AIMs and high gamma power to varying degrees, while the serotonin 1A antagonist WAY100635 reversed these effects. Unexpectedly, as cortical high gamma power increased, phase locking of cortical pyramidal spiking to high gamma oscillations decreased, raising questions regarding the neural substrate(s) responsible for high gamma generation and the functional correlation between high gamma and dyskinesia.