The Distinct Electrophysiological Mechanisms in the Cortico-Striatal Circuit of LID Rats

Levodopa-induced dyskinesia (LID) is a severe motor complication associated with long-term levodopa (L-DOPA) treatment for Parkinson's disease (PD). Its underlying mechanisms remain unclear, and candidate biomarkers lack consistency. To investigate cortico-striatal network alterations associated with LID, we simultaneously recorded single-neuron spikes and local field potentials (LFPs) from the dorsolateral striatum (DLS) and the primary motor cortex (M1) in LID rats. Our results showed that in the DLS, the LID group had a greater number of putative fast-spiking interneurons (FSIs) with lower firing rates, and fewer putative medium spiny neurons (MSNs) with higher firing rates. In M1, pyramidal neurons were fewer but fired faster, while interneurons were more numerous with no change in firing rate. Although gamma power increased and delta power decreased in both regions in LID rats, delta-gamma phase-amplitude coupling (PAC) was present in the DLS but absent in M1. Furthermore, cross-regional PAC analysis revealed significantly stronger coupling between the low-frequency phase of M1 and the high-frequency amplitude of the DLS than in the opposite direction, indicating an asymmetric pattern of cortico-striatal coupling in LID. These findings demonstrate region-specific alterations in neuronal activity and oscillatory coupling associated with LID and suggest that asymmetric cortico-striatal PAC may serve as a promising electrophysiological marker for characterizing abnormal network dynamics underlying dyskinesia.