Another limitation of hiPSC studies is that connections between neurons are inherently random, unlike neuronal networks that form in vivo. Micropatterning and microfluidic devices offer a potential solution for organizing circuits and exercising granular control over the cells’ microenvironment (for review, see Brunello et al., 2013). Microfluidic local perfusion chambers have been successfully implemented with dissociated primary neurons from rodents. For example, a microfluidic local perfusion chamber has been developed to manipulate distinct synaptic regions, directing synapse formation in distinct parallel rows through microgrooves connecting two distinct neuronal populations (Taylor et al., 2010). hiPSC-derived neurons are compatible with micropatterning for long term growth and circuit organization. Neurons adhere to regularly spaced adherent surfaces with neurites crossing cell-repellant surfaces to form connections (Burbulla et al., 2016). This system facilitates long-term studies of mitochondrial dynamics, axonal transport, and dynamic network formation (Burbulla et al., 2016). Compartmentalized microfluidic devices have been utilized to create interconnections between excitatory, inhibitory, and dopaminergic hiPSC-derived neurons, mimicking reward circuits (Fantuzzo et al., 2017). This is a key development for studying AUDs, considering accumulating evidence pointing towards differential reward processing in alcohol dependent individuals (Kamarajan et al., 2006, 2015; Müller-Oehring et al., 2013).
