Re-expression of IQSEC2 isoform 1 rescues the impaired synaptic transmission in the pyramidal neurons in layer 5 of the mPFC in IQSEC2 KO mice. (A) Schematic diagram for AAV vectors used for IQSEC2 rescue, control, and EGFP marker (left). Representative confocal microscopic images of AAV-injected brain slice containing both hemispheres of mPFC. Scale bar = 0.5 mm. (B) Sample traces and summary graphs for mEPSCs in wild-type infected with control AAV (WT Control), IQSEC2 KO infected with control AAV (KO Control), and IQSEC2 KO infected with IQSEC2 AAV (KO Rescue) pyramidal neurons in layer 5 of the mPFC. The decreased frequency of mEPSCs in IQSEC2 KO neurons is recovered in KO Rescue neurons. (C) Sample traces and summary graphs for mIPSCs in wild-type infected with control AAV (WT Control), IQSEC2 KO infected with control AAV (KO Control), and IQSEC2 KO infected with IQSEC2 AAV (KO Rescue) pyramidal neurons in layer 5 of the mPFC. The decreased frequency of mIPSCs in IQSEC2 KO neurons is rescued in KO Rescue neurons. (D) Sample traces and summary graph for the paired-pulse ratio of evoked AMPA EPSCs in wild-type infected with control AAV (WT Control), IQSEC2 KO infected with control AAV (KO Control), and IQSEC2 KO infected with IQSEC2 AAV (KO Rescue) pyramidal neurons in layer 5 of the mPFC. The increased paired-pulse ratio is restored to the wild-type level in the KO Rescue neurons. (E) Sample traces and summary graph for evoked AMPA EPSC in wild-type infected with control AAV (WT Control), IQSEC2 KO infected with control AAV (KO Control), and IQSEC2 KO infected with IQSEC2 AAV (KO Rescue) neurons. The decreased amplitude of AMPA EPSC is recovered in the KO Rescue neurons. (F) Sample traces and summary graph for evoked GABA IPSC in wild-type infected with control AAV (WT Control), IQSEC2 KO infected with control AAV (KO Control), and IQSEC2 KO infected with IQSEC2 AAV (KO Rescue) neurons. The decreased amplitude of GABA IPSC is recovered in the KO rescue neurons. (G) Sample traces and summary graph for the NMDA/AMPA ratio in wild-type infected with control AAV (WT Control), IQSEC2 KO infected with control AAV (KO Control), and IQSEC2 KO infected with IQSEC2 AAV (KO Rescue) neurons. The increased NMDA/AMPA ratio is restored in KO Rescue neurons. Data are means ± SEM (numbers of neurons/independent animals examined are shown in graphs). Statistical analyses were performed by One-way ANOVA followed by Bonferroni post-hoc test (* p < 0.05; ** p < 0.01; n.s. = not significant. Data values used in graphs are shown in Tables S2 and S4.