Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Dyskinesia is Closely Associated with Synchronization of Theta Oscillatory Activity Between the Substantia Nigra Pars Reticulata and Motor Cortex in the Off L-dopa State in Rats

Excessive theta(θ)frequency oscillation and synchronization in the basal ganglia(BG)has been reported in elderly parkinsonian patients and animal models of levodopa(L-dopa)-induced dyskinesia(LID),particularly theθoscillation recorded during periods when L-dopa is withdrawn(the off L-dopa state).To gain insight into processes underlying this activity,we explored the relationship between primary motor cortex(M1)oscillatory activity and BG output in LID.We recorded local field potentials in the substantia nigra pars reticulata(SNr)and M1 of awake,inattentive resting rats before and after L-dopa priming in Sham control,Parkinson disease model,and LID model groups.We found that chronic L-dopa increasedθsynchronization and information flow between the SNr and M1 in off L-dopa state LID rats,with a SNr-to-M1 flow directionality.Compared with the on state,θoscillational activity(θsynchronization and informationflow)during the off state were more closely associated with abnormal involuntary movements.Our findings indicate thatθoscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1θoscillation may participate in the induction of dyskinesia.