gms | German Medical Science

Objective: Parkinson's disease (PD) is a neuro-degenerative pathology affecting the basal ganglia through a progressive necrosis of dopaminergic cells. As a consequence, it produces altered information patterns along movement-related ganglia-mediated pathways in the brain, thus inducing motor disorders like tremor at rest and postural instability. While pharmacological and electrical therapies are currently available for PD treatment, the mechanisms according to which such disease operates are still partly unclear, due to the lack of knowledge about the basal ganglia role in motor tasks execution. For that reason, our work aims at investigating the inner dynamics of the basal ganglia and reproducing how PD alters their electric patterns.

Methods: We develop a two-stages modeling study: we firstly focus on those nuclei involved in the genesis of PD motor symptoms (in particular, STN, GPi and GPe) and, for them, develop a conductance-based electrical model able to mimic quantitative data from different in vitro physiological analyses. Then, cellular models are inserted in a network scheme to reproduce the main actual anatomical connections.

Results: Our models show that several highly nonlinear electrical behaviors can stem from the interaction between specific ionic currents as particular parameters change. The network connections, instead, reproduce some of the macroscopic behaviors reported in literature for normal and Parkinsonian conditions, and indicate that topology and feedback links are required for synchronization purposes along the network.

Conclusions: The proposed simulation study reproduces nonlinear dynamics occurring into the subthalamo-pallidal neurons and mimics the actual synaptic connections in order to investigate the mechanisms generating the pathological neural activity in PD conditions. Results match experimental data both from human subjects and primates and suggest that synchronization across the basal ganglia maybe is one of the main disruptive effects of the disease.