Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

Motor symptoms of Parkinson's Disease (PD) are associated with dopamine deficits and pathological oscillation of basal ganglia (BG) neurons in the beta range ([12-30] Hz). However, how dopamine depletion affects the oscillation dynamics of BG nuclei is still unclear. With a spiking neurons model, we here capture the features of BG nuclei interactions leading to oscillations in dopamine-depleted condition. We highlight that both the loop between subthalamic nucleus (STN) and Globus Pallidus pars externa (GPe) and the loop between striatal fast spiking and medium spiny neurons and GPe display resonances in the beta range, and synchronize to a common beta frequency through interaction. Crucially, the synchronization depends on dopamine depletion: the two loops are largely independent for high levels of dopamine, but progressively synchronize as dopamine is depleted due to the increased strength of the striatal loop. The model is validated against recent experimental reports on the role of cortical inputs, STN and GPe activity in the generation of beta oscillations. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustained beta oscillations in PD subjects, and explain how this interplay depends on the level of dopamine. This paves the way to the design of therapies specifically addressing the onset of pathological beta oscillations. Author summaryPD is associated with the death of neurons generating a particular neurotransmitter: the dopamine. Motor symptoms of PD, on the other hand, are known to be due to dysfunctions in a particular subcortical area of the brain: the BG network. In particular, the BG network develops pathological oscillations in the beta ([12-30] Hz) frequency range. What is unclear is the mechanism through which dopamine depletion leads to these oscillations. In this work we developed a BG network model and we found that the actual reason for these abnormal oscillations is the synchronization of two loops within the network that are individually oscillating in the beta range. For high levels of dopamine the two loops are decoupled and the oscillation power is low. Conversely. when dopamine is depleted (as in PD) the two loops synchronize and originate the pathological oscillations associated with motor symptoms.