Bringing cellular clarity to the cortical component of <scp>ALS</scp> with a high‐density multi‐electrode array system

There is selective vulnerability in diseases, requiring the understanding of cell-type specific aspects of neurodegeneration with cellular resolution. Single-cell electrophysiology enables direct investigation of neuronal excitability, ion-channel dynamics, and synaptic transmission with high temporal precision, which is crucial in understanding neuronal circuitries and how they are affected in diseases. Microelectrode arrays (MEAs) have emerged as powerful platforms enabling long-term, parallel, and non-invasive extracellular measurements. The advent of complementary-metal-oxide-semiconductor (CMOS)-based and high-density microelectrode arrays (HD-MEAs) has expanded the spatial and temporal resolution attainable both in vitro and ex vivo. Combined with acute slices, novel cell-culture approaches and three-dimensional (3D) brain organoids, these tools now expedite translational research in disease modeling, neurotoxicity, and pharmacology. Here, we summarise the significance of single-cell electrophysiology, the advantages of the MEA systems, and the latest biomedical and technological advances in this area of research.