Extended Data Fig. 4: Intrinsic electrophysiology of Scn2a+/KI and CRISPRa treated neurons.
From: CRISPR activation for SCN2A-related neurodevelopmental disorders
a. AP threshold from P57-85 Scn2a-rAAV-empty vector Scn2a+/+ (light gray) and Scn2a+/− (magenta) neurons, Scn2a-rAAV-CRISPRa treated Scn2a+/+ (dark gray) and Scn2a+/− (purple) neurons, and Scn2a+/KI Cre- (green) and Scn2a+/KI Cre+ (gray) neurons. Threshold of the first AP evoked by a near-rheobase current. Scn2a+/+ + empty: n = 17 cells; Scn2a+/− + empty: n = 27 cells; Scn2a+/+ + CRISPRa: n = 24 cells; Scn2a+/− + CRISPRa: n = 19 cells; Scn2a+/KI Cre-: n = 29 cells; Scn2a+/KI Cre + : n = 21 cells. No significant differences. Holm-Šídák multiple comparisons test. Circles are individual cells, box plots are medians, quartiles and 100% tails. b. Input resistance (MΩ). Scn2a+/+ + empty: n = 17 cells; Scn2a+/− + empty: n = 27 cells; Scn2a+/+ + CRISPRa: n = 17 cells; Scn2a+/− + CRISPRa: n = 11 cells; Scn2a+/KI Cre-: n = 26 cells; Scn2a+/KI Cre + : n = 19 cells. No significant differences. Holm-Šídák multiple comparisons test. Circles are individual cells, box plots are medians, quartiles and 100% tails. c. Rheobase current (pA) to generate first spike. Scn2a+/+ + empty: n = 16 cells; Scn2a+/− + empty: n = 27 cells; Scn2a+/+ + CRISPRa: n = 17 cells; Scn2a+/− + CRISPRa: n = 12 cells; Scn2a+/KI Cre-: n = 25 cells; Scn2a+/KI Cre + : n = 19 cells. No significant differences. Holm-Šídák multiple comparisons test. Circles are individual cells, box plots are medians, quartiles and 100% tails. d. APs per 300 ms stimulation epoch for each current amplitude. Left: Quantification of firing rate slope of data on Right. Scn2a+/+ + empty: n = 16 cells; Scn2a+/− + empty: n = 27 cells; Scn2a+/+ + CRISPRa: n = 17 cells; Scn2a+/− + CRISPRa: n = 12 cells; Scn2a+/KI Cre-: n = 25 cells; Scn2a+/KI Cre + : n = 19 cells. No significant differences. Holm-Šídák multiple comparisons test. Circles are individual cells, box plots are medians, quartiles and 100% tails.Right: Number of APs versus current amplitude injected. Circles and bars are mean ± SEM at each stimulus intensity.
