The above investigations demonstrate the utility of patient hiPSC-derived neurons for modeling cellular interactions, gaining insight in the impact of a given mutation on said interactions, and elucidating the molecular mechanisms responsible. Most importantly, this is achieved using human cells, thus providing much more translational value than animal models. Despite these advantages, a number of issues surround induced neural protocols (see Engel et al., 2016), especially in the context of modeling synaptogenesis and network dysfunction. First, gene expression studies indicate hiPSC neurons best resemble fetal brain tissue (Brennand et al., 2015). Second, hiPSC neurons require extensive cultivation periods of up to 7 months (Maroof et al., 2013; Nicholas et al., 2013; Suzuki and Vanderhaeghen, 2015). Moreover, pure neuronal cultures are limited in their ability to accurately re-capitulate network functionality, since glial cells play an important role in regulating neuronal activity and establishing myelination.
