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 β 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 β range, and synchronize to a common β 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 β oscillations. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustained β 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 β oscillations

Beta oscillators interplay in a model of parkinsonian Basal Ganglia

The work will be presented in five main Chapters: in the first one I introduce the main properties of the network of the Basal Ganglia and I present an overview of the results obtained by a collection of previous works on the role of Dopamine depletion and the onset of beta activity. Afterwards, Chapter 2 is devoted to main concepts and tools that are employed throughout the thesis: particularly, I summarize the structure and functionalities of neuronal cells, I describe their mathematical modelization and I present the model of the network that will be used throughout the thesis. Besides that, because of their prominent role in the following part of the work, a review of the concept of synchronization and a presentation of the main tools for spectral and numerosity analysis is proposed in this section. Following, in Chapter 3, I present the more specific methods that I purposefully designed in order to deepen the properties of the employed model. After a brief overview of the main features of the implemented code, the remaining part of the chapter is devoted to the description of the deployed methods in order to detect the main sources of beta activity and to study the properties of the system as a function of: - the intensity of the coupling between the main detected beta oscillators; - the introduction of additional non-beta perturbations; - the modelization of the severity of the condition of dopamine depletion. In Chapter 4, I report the results of the performed analysis, with a focus on the processes through which the two main oscillators in the beta-regime merge together and consequently generate a comprehensive and robust oscillator. Finally, in the conclusive chapter of this thesis I propose possible further investigations that could follow from my work and I suggest some potential applications of the obtained results in their relation to the actual cutting edge technologies employed in the therapies of Parkinson's disease