INVESTIGATION OF POSSIBLE INTERACTIONS BETWEEN BASAL GANGLIA LOOPS AND CEREBELLAR NETWORK IN THE 6-OHDA MODEL OF IDIOPATHIC PARKINSON'S SYNDROME

My PhD research investigates interactions between the cerebellum and basal ganglia in Parkinson’s disease (PD) and its major treatment-related complication, L-DOPA-induced dyskinesia (LID). Although these structures have been studied as independent motor systems, growing evidence indicates that they communicate via indirect and possibly direct pathways. These interactions may contribute both to compensation for motor deficits and to the progression of pathological symptoms. To address this, I use the unilateral 6-hydroxydopamine (6-OHDA) rat model of PD. I combine in vivo electrophysiological recordings from the deep cerebellar nuclei, basal ganglia, and motor cortex with synchronized behavioral tracking. This approach allows me to examine how network oscillations evolve across disease stages and during chronic L-DOPA treatment. A central aim is to determine how cerebellar output contributes to the abnormal beta and gamma oscillations characteristic of PD and LID, respectively.
In the second part of the project, I apply a dual viral chemogenetic strategy to selectively inhibit the cerebello-thalamic pathway, targeting projections from the deep cerebellar nuclei to the parafascicular thalamus. This enables transient disruption of cerebellar–basal ganglia communication and assessment of its causal role in dyskinesia. By comparing electrophysiological and behavioral measures before and after inhibition, I aim to identify when cerebellar influence shifts from compensatory to maladaptive.
Understanding this transition may reveal new circuit-level therapeutic targets to restore balanced motor network activity in PD.