Figure 3.

Hypersensitivity of mutant SST interneurons to depolarization block during seizure-like activity. A-D, Representative example traces of WT (A; black), Scn8a^D/+ (B; red), and Scn8a-SST^W/+ (C; green) SST-pyramidal neuron pairs exposed to bath solution containing 0 Mg²⁺, 50 μm 4-AP (A-C) and WT SST-pyramidal neuron pairs exposed to 0 Mg²⁺, 100 μm 4-AP (D; blue). Expanded views represent example synchronous SST interneuron depolarization block and pyramidal neuron ictal discharge events (B-D), which were not present in most neuronal pairs in the control group (A). E, Cumulative distribution plot of seizure-like events over time reveals that Scn8a^D/+ + 0 Mg²⁺; 50 μm 4-AP (red), Scn8a-SST^W/+ + 0 Mg²⁺; 50 μm 4-AP (green), and WT + 0 Mg²⁺; 100 μm 4-AP (blue) were hypersensitive to depolarization block-mediated seizure-like events relative to WT + 0 Mg²⁺; 50 μm 4-AP neuron pairs (black; **p < 0.01; Log-rank Mantel-Cox test).