Fig. 2: At 7 weeks, IQSEC2-mutant neurons start to decrease excitability while control neurons increase excitability compared to the earlier time point.

a A representative trace of evoked action potentials in the current-clamp mode of control (upper graph) and IQSEC2-mutant (lower graph) neurons. b The total number of evoked action potentials is similar on average between IQSEC2-mutant and control neurons. c The maximum number of evoked action potentials is similar between IQSEC2-mutant and control neurons. d Representative traces of a control (upper graph) and IQSEC2-mutant (lower graph) action potentials. The first action potential with minimal injected current is plotted. e The amplitude of the fast AHP is larger in IQSEC2-mutant neurons than in control neurons. f The spike amplitude is similar between IQSEC2-mutant neurons and control neurons. g The spike width is narrower in IQSEC2-mutant neurons than in control neurons. h The threshold for eliciting an action potential is not different between IQSEC2-mutant and control neurons. i The cell capacitance is not different between IQSEC2-mutant and control neurons. j Representative traces of sodium and potassium currents recorded in voltage-clamp in control (upper graph) and IQSEC2-mutant (lower graph) neurons. k The average sodium currents in IQSEC2-mutant neurons are increased compared to control neurons. l The average slow potassium currents in IQSEC2-mutant neurons are increased compared to control neurons. m The average fast potassium currents are increased in IQSEC2-mutant compared to control neurons. n A heatmap of the differentially expressed genes (by RNA sequencing) between control (3 biological replicates) and IQSEC2-mutant neurons (one sample derived from clone 1 and one sample derived from clone 3). o Significant gene ontology (GO) terms (Biological processes) that were downregulated in IQSEC2-mutant neurons. p Functional categories that were downregulated in IQSEC2-mutant neurons. q Functional categories that were upregulated in IQSEC2-mutant neurons. r Significant gene ontology (GO) terms (Biological processes) that were upregulated in IQSEC2-mutant neurons. s A screenshot of KCNA5 expression; (from the top track down): control sample 1, control sample 2, control sample 3, IQSEC2-mutant clone 1, IQSEC2-mutant clone 3 (s). KCNA5 expression is significantly greater in IQSEC2-mutant neurons compared to the control neurons. The data was collected using a Wiggle plot with a step size of 2 bp. In this figure asterisks represent statistical significance by the following code: *p value < 0.05, ****p < 0.0001. Error bars represent the standard error in this figure.