Nadadhur AG, Emperador Melero J, Meijer M, Schut D, Jacobs G, Li KW, Hjorth JJJ, Meredith RM, Toonen RF, Van Kesteren RE, Smit AB, Verhage M, Heine VM
PLoS ONE 12 (6) e0178533 [2017-06-06; online 2017-06-06]
Generation of neuronal cultures from induced pluripotent stem cells (hiPSCs) serve the studies of human brain disorders. However we lack neuronal networks with balanced excitatory-inhibitory activities, which are suitable for single cell analysis. We generated low-density networks of hPSC-derived GABAergic and glutamatergic cortical neurons. We used two different co-culture models with astrocytes. We show that these cultures have balanced excitatory-inhibitory synaptic identities using confocal microscopy, electrophysiological recordings, calcium imaging and mRNA analysis. These simple and robust protocols offer the opportunity for single-cell to multi-level analysis of patient hiPSC-derived cortical excitatory-inhibitory networks; thereby creating advanced tools to study disease mechanisms underlying neurodevelopmental disorders.