A Multi-Electrode Array Platform for Modeling Epilepsy Using Human Pluripotent Stem Cell-Derived Brain Assembloids

In the past few decades, an explosion of gene discovery has identified hundreds of genes that cause or are associated with epilepsy. However, the pathogenic mechanisms are not as well explored. Our laboratory studies how genetic changes affect early brain development and result in brain malformations and epilepsy, a debilitating disease characterized by chronic seizures.

Genetic epilepsies have been typically studied using animal models, including mice, zebrafish, drosophila, and rabbits. Human stem cells have more recently been used to model genetic epilepsies as techniques to differentiate stem cells into neuro tissue have advanced. With the advent of brain organoids, you can recapitulate structure aspects of brain development.

Measuring electrophysiological activity and determining biomarkers of epilepsy related activity from brain organoids and assembloids is challenging. Partly, this technique is limited because brain organoids cannot have seizures like an intact animal can. Nonetheless, finding electrophysiological differences in this in vitro model and responses to drug treatments may help determine pathological mechanisms and therapeutic responses in genetic epilepsies.

Electrophysiological activity can be assessed using traditional patch climb recordings, local field recordings with electrodes, and optical techniques like calcium and memory voltage imaging. Using multielectrode array recordings has the advantage of being able to do launch two recordings over time and recording from multiple locations of an assembloid simultaneously.