We do not at present understand what determines the ability of a neuron to form synapses. Most neuron-like cells can produce action potentials and elaborate postsynaptic specializations – even non-neuronal cells can be made to generate postsynaptic specializations by simple expression of postsynaptic cell-adhesion molecules (Biederer et al., 2002) – but the ability to form presynaptic specializations seems to be specific for a ‘real’ neuron (Yang et al., 2011). Ngn2-induced iN cells form robust synapses among themselves when cultured in the presence of mouse astrocytes (which supply unknown synaptogenic factors) in a manner that was not previously observed for any human iN cells, and occurs much faster than during conventional guided ES/iPS cell differentiation approaches. The synapses that are thus generated exhibit full function and are capable of short-term plasticity and direct modulation by retinoic acid, suggesting that Ngn2 iN cells provide a useful system for studies in which the effects of mutations or pharmacological agents on synaptic transmission in human neurons is investigated.
