Abstract
Levodopa is the gold-standard treatment for Parkinson's disease, but chronic use results in levodopa-induced dyskinesia (LID) in approximately 80% of patients. Previous research has identified critical network changes in the cortico-basal ganglia pathway associated with LID; however, no study has extensively recorded motor thalamus single-cell activity in a LID model. The motor thalamus is a key node in the movement pathway, receiving basal ganglia and cerebellar inputs and projecting an integrated signal to the motor cortex, therefore could be a critical site for LID pathophysiology. The current study investigated single-cell and population motor thalamus activity following LID using extracellular electrophysiology. Activity was compared across control and parkinsonian rats, and then Parkinsonian rats that had or had not developed LID following chronic levodopa treatment. Baseline Mthal activity in the LID rat was hyperactive, bursty, and synchronised. Similar but weaker trends were found in Parkinsonian and non-dyskinetic rats. Following acute levodopa administration, motor thalamus activity changed greatly in the LID rat, showing increased firing rate and bursts, while decreasing oscillation strength, LTS burst number, and synchronisation. The non-dyskinetic rat showed opposing changes, hinting at a critical switch in motor thalamus activity associated with LID onset and not long-term levodopa treatment. These results show critical changes in Mthal activity following LID onset, whereby the motor thalamus becomes hyperactive and disorganised in LID. This study expands on previous observations of network changes in the corticobasal ganglia pathway, showing that motor thalamus activity contributes to LID pathophysiology.