The potential of in vitro neuronal networks cultured on micro electrode arrays for biomedical research

In vitro neuronal models have become an important tool to study healthy and diseased neuronal circuits. The growing interest of neuroscientists to explore the dynamics of neuronal systems and the increasing need to observe, measure and manipulate not only single neurons but populations of cells pushed for technological advancement. In this sense, micro-electrode arrays (MEAs) emerged as a promising technique, made of cell culture dishes with embedded micro-electrodes allowing non-invasive and relatively simple measurement of the activity of neuronal cultures at the network level. In the past decade, MEAs popularity has rapidly grown. MEA devices have been extensively used to measure the activity of neuronal cultures mainly derived from rodents. Rodent neuronal cultures on MEAs have been employed to investigate physiological mechanisms, study the effect of chemicals in neurotoxicity screenings, and model the electrophysiological phenotype of neuronal networks in different pathological conditions. With the advancements in human induced pluripotent stem cells (hiPSCs) technology, the differentiation of human neurons from the cells of adult donors became possible. hiPSCs-derived neuronal networks on MEAs have been employed to develop patient-specific in vitro platforms to characterize the pathophysiological phenotype and to test drugs, paving the way towards personalized medicine. In this review, we first describe MEA technology and the information that can be obtained from MEA recordings. Then, we give an overview of studies in which MEAs have been used in combination with different neuronal systems (i.e. rodent 2D and three-dimensional (3D) neuronal cultures, organotypic brain slices, hiPSCs-derived 2D and 3D neuronal cultures, and brain organoids) for biomedical research, including physiology studies, neurotoxicity screenings, disease modeling, and drug testing. We end by discussing potential, challenges and future perspectives of MEA technology, and providing some guidance for the choice of the neuronal model and MEA device, experimental design, data analysis and reporting for scientific publications.