In the present study, we describe a new, highly effective method that generates a homogeneous population of iN cells by forced expression of a single transcription factor in ES or iPS cells. We demonstrate that the new method results in the reproducible generation of the same type of neuron with quantitatively the same properties independent of the ES or iPS cell line used. The entire procedure generates iN cells in only a few weeks, allowing a rapid turnaround of experiments, and the resulting iN cells exhibit short-term plasticity, are modulated at the level of their synapses, and integrate into neuronal networks when transplanted into the mouse brain. Moreover, the new iN cells can be used for studying synaptic properties including plasticity, for large-scale Ca2+-imaging for example for drug screening purposes, and for disease modeling as exemplified in our Munc18-1 KD experiments. Thus, we believe that the approach described here has the potential to enable mechanistic and translational studies on human neurons that exceed currently existing capabilities, and hope that the simplicity of the approach will allow its wide dissemination. Table
