High-throughput electrophysiological phenotyping of synthetic Parkinson patient-specific nigrostriatal microcircuits

Most cases of Parkinson’s Disease (PD) are due to unknown causes, preventing the development of curative treatments. Rare heritable PD caused by mutations in single genes has been studied as a model of the general sporadic form. Previous studies support this approach as heritable and sporadic PD share common molecular defects. This project aims to link the causal factors of sporadic cases with the ones present in genetically-driven cases.

I propose to study how different PD-related molecular defects influence the way neurons affected in PD communicate with each other. As a proof of concept, I will use stem cells derived from healthy controls and from patients bearing two mutations affecting different cellular functions. They will be grown on an innovative microchip capable of both converting the stem cells into the different neuron types affected in PD and of recording the resulting neuronal communication. The diverse parameters measured will be analyzed with advanced computational methods to determine how each mutation affects neuronal communication.

This process will be capable of assigning molecular defects to sporadic PD according to which communication defects are observed in patients’ neurons. Classifying the different molecular defects in PD in this way will provide a platform with unprecendented potential to help find a cure for all PD patients.