Funded by: NWO Nonlinear Dynamics in Natural Systems, MIRA Institute
PhD: Bettina Schwab
Supervisor: Stephan van Gils, Richard van Wezel
Collaboration: Biomedical Signals and Systems, UTwente
Parkinson's disease (PD) is a frequent neurodegenerative disorder strongly affecting the patient's life. While there is currently no cure, treatment of the symptoms is possible via medication with L-Dopa and/or deep brain stimulation. However, these treatments often only lead to partial relief of the symptoms and usually come along with severe side effects.
The decline of motor and cognitive skills may arise from a pathological behavior of neural networks in the basal ganglia-thalamocortical circuit. In PD patients, abnormal high levels of synchronization and bursting have been found and oscillations change their frequency bands. Many people believe in a link between these network abnormalities and the occurrence of tremor, akinesia and bradykinesia.
Up to now, the causes and mechanisms of this abnormal behavior in the affected neural networks are unknown. Also the mechanism of deep brain stimulation is still a matter of debate.
In this project, we combine experiments of imaging and electrophysiology with computational modeling to get a better understanding of the pathological network activity in Parkinson's disease. In particular, we quantify the expression of gap junctions in the basal ganglia by confocal microscopy and in acute slice preparations. We investigate the impact of gap junctions, leading to electrical coupling between neurons, in computational models of the basal ganglia.
Confocal image of rat brain tissue from the putamen. Green: WGA, labeling cell membranes and extracellular space compartments; blue: DAPI, labeling cell nuclei; red: Cx36, labeling a type of neuronal gap junctions
The experiments serve as a basis to improve computational models of the basal ganglia with the aim of a better understanding of the basic mechanisms of PD. This may in later stages lead to refined and new treatments such as specific stimulation protocols for deep brain stimulation or novel drugs.