To explore the potential use of ES- or iPS-cell derived iN cells for monitoring drug activities, studying human synaptic plasticity, or modeling human disease states, we examined Ngn2 iN cells in a variety of paradigms. We first tested the use of optogenetics to directly probe the formation of presynaptic specializations of iN cells onto co-cultured mouse neurons (Figs. 5A–5C). When we selectively expressed the channelrhodopsin variant CHIEF in iN cells and co-cultured the iN cells with mouse neurons, we found that this approach led to an accurate definition of presynaptic function in the human iN cells that allows measurement of synaptic transmission between two connected neurons without the need to separately patch these neurons.
