Buspirone regulates cortico-striatal gamma oscillations to ameliorate dyskinesia

BackgroundLevodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is linked to exaggerated gamma oscillations. Buspirone, a 5-HT1A receptor agonist, is a potent medication for psychiatric conditions, predominantly prescribed for anxiety treatment.ObjectiveThis study aims to investigate whether buspirone alleviates dyskinesia in LID rat and its effects on pathological oscillatory activity and cortico-striatal functional connectivity.MethodsWe collected motor behavior and electrophysiological data of cortico-striatal from Sham rats, unilateral 6-hydroxydopamine (6-OHDA)-lesioned PD model rats, and rats with LID. We further examined the behavioral and electrophysiological changes in LID rats following buspirone intervention.ResultsPD rats showed increased beta activity and aperiodic components at 10-50 Hz, while LID rats exhibited excessive gamma oscillations and aperiodic activity at 50-150 Hz. Additionally, gamma-band functional connectivity within the cortico-striatal circuit was significantly enhanced during on-state dyskinesia, when rats exhibited abnormal involuntary movements. Administration of buspirone effectively reduced dyskinesia severity, suppressed gamma activity, decreased aperiodic components (50-150 Hz), and disrupted gamma-band functional connectivity without compromising the antiparkinsonian effects of levodopa.ConclusionsExcessive gamma oscillations represent a key electrophysiological marker of dyskinesia. Altered gamma-band connectivity within the cortico-striatal network may contribute to its pathophysiology. Buspirone appears to be a promising candidate for the treatment of LID, potentially offering a novel therapeutic strategy.