Fig. 8

Functional differences in neurons derived from these models were assessed by current clamp analysis. a–c Action potentials elicited by three different 800 msec depolarizing current injections in iPSC-derived cExNs from the UC-M, UM, and AP models. b Exponential fits (smooth curves) indicate significantly fewer action potentials elicited on average by current injections up to 120 pA in neurons derived from the UC-M model, by comparison with the UM and AP models (p < 0.05, F-statistic). Recordings under current clamp also revealed c a more depolarized threshold for action potential initiation in UC-M-derived neurons compared with both UM- and AP-derived models and d a higher initial spike frequency in UC-M compared with UM-derived neurons. e–g UM-derived neurons exhibited a significantly higher e maximal number of spikes and f first spike amplitude, and a G briefer first spike half-width than UC-M or AP neurons. h-i Compared to UC-M and UM neurons, AP-derived neurons exhibited h a substantially lower rheobase and I a more significant decline in average action potential peak amplitude with each succeeding spike (a and i). Plots show combined data from cExNs and cINs (n = 3). P < 0.05 was defined by 2-way ANOVA on ranks with post hoc Student-Newman-Keuls test. A complete summary of the physiological recordings performed is also provided in Additional file 13