We next investigated whether assembled hSS-hCS could be used to model migration defects. Previous work in rodents has indicated that L-type calcium channels (LTCCs) play a critical role in interneuron migration by regulating saltation frequency and migration termination17. LTCCs have been repeatedly associated with neuropsychiatric disease22,23, and gain-of-function mutations in the LTCCs-encoding CACNA1C gene lead to Timothy syndrome (TS)– a severe neurodevelopmental disorder characterized by autism spectrum disorder and epilepsy24,25. We generated hSS and hCS from hiPSCs from 3 patients with TS carrying the recurrent p.G406R substitution (Fig. 3a) and compared them to 4 control subjects (Extended Data Fig. 9a, b; Supplementary Table 1). We did not observe defects in the differentiation of TS hiPSC lines into hSS (Extended Data Fig. 9c–g). Calcium imaging showed increased residual calcium following depolarization in hSS-derived TS neurons, as well as in hCS-derived TS neurons compared to control cells (Fig. 3b; Extended Data Fig. 9h, i), similar to what we have previously shown in TS hiPSC-derived glutamatergic neurons26. We investigated the migration of Dlxi1/2b::eGFP+ cells in fused hSS-hCS (Fig. 3c; Extended Data Fig. 9j;
