Finally, we explored whether the GABAergic iN cells can be used to study inhibitory synapse function and uncover cellular phenotypes of a disease condition. Collybistin is a core component of inhibitory postsynapses and regulates the submembrane clustering of GABAARs20,21. Loss-of-function mutations in collybistin have been associated with X-linked mental disorder, epilepsy and hyperekplexia22,23. We performed shRNA-mediated knockdown (KD) of collybistin in iN cells using five shRNA constructs, and this KD resulted in significant reduction in collybistin expression with variable efficiencies (Fig. 4a and Supplementary Fig. 9). Strikingly, collybistin KD constructs caused a reduction of peak amplitude and total charge transfer of IPSCs upon local GABA administration (Fig. 4b–d), which suggested that expression level of collybistin directly affects the number of surface GABA receptors in human neurons. Next, we quantified inhibitory synaptic properties and found a reduction of both amplitude and frequency of spontaneous IPSCs in iN cells following collybistin KD (Fig. 4e–g). This effect was specific for inhibitory synapses, as there was no change in spontaneous EPSCs or intrinsic membrane properties (Supplementary Fig. 9). These findings are similar to findings
