Objective: To study the abnormal striatal oscillations and regulation of striatal oscillatory activities by micro-infusion of glutamate receptor antagonist in the non-human primate model of parkinsonism.

Background: Dopamine depletion in Parkinson’s disease (PD) has been associated with abnormal oscillatory activities in the cortico-basal ganglia network (i.e. cortex, globus pallidus, and subthalamic nucleus). However, oscillatory activity in the striatum following dopamine loss and chronic replacement therapy remains poorly defined. In the current study, striatal local field potentials (LFPs) were recorded during “off”, “on” and “on-with-dyskinesia” states in advanced parkinsonian primates. Additionally, glutamate receptor antagonist known to stabilize neuronal firing changes after L-dopa administration was used to regulate the abnormalities in striatal activity.

Methods: Striatal LFPs were recorded in MPTP-treated monkeys with standard techniques. The NMDA receptor antagonist LY235959 was injected into the striatum at the recording site before the systemic injection of levodopa. Striatal LFPs were analyzed during “off”, “on” (after local artificial CSF or NMDA antagonist and systemic levodopa administration), and subsequently during “on”-with-dyskinesia states.

Results: A peak with the higher amplitude (relative power) in the 8-13 Hz (alpha frequency band) was observed in the “off” state. This peak significantly decreased in the “on” state (local aCSF and LY235959). However, a peak with higher amplitude in the 13-20 Hz (low-beta frequency band) was observed during “on” state. The NMDA antagonist reduced the peak amplitude in 13-20 Hz during the “on” state. No clear peak was observed in relation to dyskinesia.

Conclusions: Results indicate that the dopamine response in parkinsonian primates is associated with a reduced peak in 8-13 Hz and an increased peak in 13-20 Hz in striatal oscillations. A reduction of glutamatergic overactivity can regulate the striatal oscillations in response to levodopa in the advanced stage of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/regulation-of-aberrant-striatal-oscillations-by-glutamate-receptor-blockade-in-parkinsonian-non-human-primates/