Probing Parkinson’s Disease with Induced Human Microcircuits on CMOS Chips

There currently are no drugs that slow down or stop the progression of Parkinson’s disease. The key limitation to understanding and treating neurodegenerative disorders such as Parkinson’s is the lack of disease models that reproduce all clinically relevant aspects of these diseases. Therefore, we will develop the technology to produce mature human neuronal microcircuits relevant to Parkinson’s disease on a multi-electrode array chip. Using the chip’s built-in recording circuitry, we will be able to compare the induced neuronal circuits of cells obtained from healthy people and from an extensive collection of Parkinson patients. This unique platform will allow us to test the role of pathogenic pathways on neuronal network dysfunction and screen for novel therapeutic approaches.

In the lab, the team implemented a workflow to produce human induced nigrostriatal circuits on high density multi-electrode array (MEA) chips to model Parkinson’s disease. Using well-validated protocols, they generated quality-controlled batches of cortical, striatal and ventral midbrain progenitor cells, which are further differentiated into cortical excitatory, medium spiny and ventral midbrain dopamine neurons on specific locations of the MEA chips. Longitudinal recordings made on circuits generated from healthy control human iPSC revealed electrophysiological features from the different neuronal subtypes, which also showed signs of functional connectivity. They are analyzing circuits obtained from mutant lines generated by the iNDi initiative.