Distinctive Effects of D1 and D2 Receptor Agonists on Cortico-Basal Ganglia Oscillations in a Rodent Model of L-DOPA-Induced Dyskinesia

Abstract

AbstractL-DOPA-induced dyskinesia (LID) in Parkinson’s disease has been linked to oscillatory neuronal activities in the cortico-basal ganglia network. We set out to examine the pattern of cortico-basal ganglia oscillations induced by selective agonists of D1 and D2 receptors in a rat model of LID. Local field potentials were recorded in freely moving rats using large-scale electrodes targeting three motor cortical regions, dorsomedial and dorsolateral striatum, external globus pallidus, and substantial nigra pars reticulata. Abnormal involuntary movements were elicited by the D1 agonist SKF82958 or the D2 agonist sumanirole, while overall motor activity was quantified using video analysis (DeepLabCut). Both SKF82958 and sumanirole induced dyskinesia, although with significant differences in temporal course, overall severity, and body distribution. The D1 agonist induced prominent narrowband oscillations in the high gamma range (70–110 Hz) in all recorded structures except for the nigra reticulata. Additionally, the D1 agonist induced strong functional connectivity between the recorded structures and the phase analysis revealed that the primary motor cortex (forelimb area) was leading a supplementary motor area and striatum. Following treatment with the D2 agonist, narrowband gamma oscillations were detected only in forelimb motor cortex and dorsolateral striatum, while prominent oscillations in the theta band occurred in the globus pallidus and nigra reticulata. Our results reveal that the dyskinetic effects of D1 and D2 receptor agonists are associated with distinct patterns of cortico-basal ganglia oscillations, suggesting a recruitment of partially distinct networks.