Modeling the Impact of Cortical Gap Junctions in Parkinson's Disease
Background and problem statement
Parkinson's disease patients show different neural activity compared to healthy subjects, including enhanced synchrony and bursting of neurons as well as oscillations in different frequency bands. While their relation to the motor symptoms of Parkinson's disease is quite established, the origin of the activity changes is still a big matter of debate.
A common hypothesis for the emergence of gamma and beta oscillations is a cortical origin. Gap junctions (direct electrical connections between cells) are known to be able to lead to oscillations, and gap junctional coupling is well described between interneurons of the cortex. Recent studies also found evidence for gap junctions between principal neurons. However, little is known about the cause for the modification of the oscillations in disease. As gap junctional coupling may be dependent on dopamine, which is depleted in Parkinson's disease, they could be a cause for modified oscillations arising in the cortex.
Main research questions:
−Can gap junctions in the cortex lead to beta/ gamma oscillations?
−Can these oscillations be modified by changing the coupling architecture and/or conductance of gap junctions to reconstruct parkinsonian conditions?
−Can the effects be explained merely by gap junctions between interneurons or are gap junctions between principal neurons necessary?
Gap junctions (green) between GABAergic neurons (red)
From Cellular Mechanisms to Neural Circuit Behavior
Principal Investigator track
Stephan van Gils / Richard van Wezel
Supervision and info
A computational model of the cortex should be developed (e. g. with the simulator BRIAN), combining both a field and a network description. The effects of gap junctional coupling in the network model should be translated into a rate function of the field model. Presumable changes of gap junctions in Parkinson's disease by dopamine depletion should be quantified and set into relation with experimental findings of oscillatory activity.
This project requires basic programming experience, handling of the simulation toolbox can be learned during the project.
Interest in basic neuroscience, neurological disease and computational modeling is highly appreciated:) The project deals with the basic understanding of Parkinson's disease and possible treatments, referring to experimental and clinical findings.
−Literature study: Gap junctions in the cortex and their modeling; effects of Parkinson's disease on the cortex
−Computational modeling of the cortex involving gap junctions
−Thesis writing, final presentation