HIPSC-differentiated dopaminergic neurons are a useful tool for studying their neurophysiology and maturation

Dopaminergic (DA) neurons play a crucial role in motor control, motivation, and cognition, with their degeneration in Parkinson's disease leading to severe motor deficits. While rodent models are widely used, species-specific differences necessitate human-relevant models. Aim. This study investigates the functional maturation of DA neurons derived from human induced pluripotent stem cells (IPS). Methods. DA differentiation was performed using a mCherry-based TH reporter iPS line. Immunocytochemistry confirmed neuronal identity, while patch-clamp recordings assessed electrophysiological properties, including firing rate, action potential duration, Ih current, and dopamine sensitivity. Results. TH expression was detected from day 10, reaching 64% by day 30. Electrophysiological maturation followed a distinct timeline, with spontaneous activity emerging around day 20 and stable pacemaking developing by day 40, along with D2 receptor-mediated autoinhibition. Conclusions. Our findings demonstrate that hIPSC-derived DA neurons attain an adult-like profile by day 40, making them a viable model for studying Parkinson's disease mechanisms and testing potential therapies. Further research will focus on slow pacemaking mechanisms in these neurons.