Fig. 3: Neurons in the Pcdh19 mosaic brain display heterogeneous excitability. | Molecular Psychiatry

Fig. 3: Neurons in the Pcdh19 mosaic brain display heterogeneous excitability.

From: Neuronal network activity and connectivity are impaired in a conditional knockout mouse model with PCDH19 mosaic expression

Fig. 3

a Cartoon showing ICV injection of AAVs in Pcdh19 floxed mice (Pcdh19fl/fl) and representative IF images of cortex (CX) and hippocampus (HP, DG region). Higher magnification images in the inserts show a couple of cortical neurons infected with GFP-Cre not expressing PCDH19 next to a couple of uninfected neurons expressing PCDH19 (in red). Scale bar, 100 µm (CX, lower magnification and HP), 40 µm (CX, higher magnification). The cartoon was created with BioRender.com. b Representative traces of APs evoked by −60, +10 and +50 pA of injected current in GFP-Cre expressing DGGCs (PCDH19-) and controls (PCDH19+) (left) and AP frequency at different current step intensities (right) from Pcdh19 floxed mice (Pcdh19fl/fl) injected with AAVs as shown in a (N DGGCs from 3 mice, PCDH19+11, PCDH19- 16; two-way ANOVA and FDR post hoc test, *p < 0.05). c AP input resistance, RMP and rheobase of neurons as in b (N DGGCs from 3 mice, PCDH19+ 11, PCDH19- 16; Student’s t-test, **p < 0.01, ***p < 0.001). d Instantaneous frequency and exponential decay slope of APs induced by 150 pA of injected current in DGGCs from mice as in b (N DGGCs from 3 mice, PCDH19+ 11, PCDH19- 16). e Representative traces of APs evoked at rheobase in PCDH19+ and PCDH19- DGGCs from mice as in b and quantification of AP threshold, amplitude, half-width, kinetic and fAHP (N DGGCs from 3 mice, PCDH19+ 11, PCDH19- 16). f Voltage-clamp experiments in PCDH19+ and PCDH19- DGGCs from mice as in b. From left to right: representative traces and current density of inward and outward currents, neuronal capacitance, activation kinetic of inward currents mediated by voltage-gated ion channels and histogram showing I/Imax at −50mV (N DGGCs from 4 mice, PCDH19+ 10, PCDH19- 15; one-sample t-test, *p < 0.05). g Representative traces and quantification of mEPSCs recorded in PCDH19+ and PCDH19- DGGCs from mice as in b (N DGGCs from 4 mice, PCDH19+ 10, PCDH19- 9). h Representative traces and quantification of mIPSCs recorded in PCDH19+ and PCDH19- DGGCs from mice as in b (N DGGCs from 4 mice, PCDH19+ 13, PCDH19- 9; Student’s t-test, *p < 0.05). All data (b–h) are shown as means ± SEM. See also Supplementary Table 3.

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