Fig. 3.

Heterozygous Scn2a knockout mice showed absence-like seizures with SWDs. a Representative traces of ECoG/EMG recordings from 10–27 weeks-old Scn2a^KO/+ (KO/+) mice (N = 6). Black arrowheads indicate the onset of SWD. Gray arrowheads indicate the onset and end of EMG suppression. b A representative trace of prolonged non-convulsive seizure. ECoG recordings detected 2 episodes of prolonged non-convulsive seizure with duration of 30–45 s in 2 out of 6 Scn2a^KO/+ mice, which were neither accompanied by convulsions, nor followed by post-ictal depression. c Representative ECoG/EMG/LFP recordings during an SWD episode in Scn2a^KO/+ mice. Epileptiform discharges with large amplitudes are seen in mPFC and CPu. Positivity was plotted up (a, b, c). d Quantification of ECoG SWDs and LFP epileptiform discharges [3-hour recording, light period, Scn2a^+/+, Scn2a^KO/+ (N = 4, each genotype)]. Mann–Whitney test, medial prefrontal cortex: U = 0, *P = 0.0286; visual cortex: U = 8, P > 0.9999; basolateral amygdala: U = 3, P = 0.2571; hippocampus CA1: U = 4, P = 0.4286; caudate putamen: U = 0, *P = 0.0286; ventroposterior thalamus: U = 7.5, P > 0.9999. e Thresholds of body temperature for hyperthermia-induced seizures did not differ between Scn2a^KO/+ and Scn2a^+/+ mice (4-week-old, N = 10, each genotype) [unpaired t-test, t(18) = 1.149, P = 0.2658]. f, g Increased seizure susceptibility to PTZ in 10-week-old Scn2a^KO/+ mice. Latencies to the first appearance of sudden immobility, myoclonus, clonic convulsion, and tonic-clonic convulsion after administrating of PTZ at doses of 50 (f, N = 20, each genotype) or 25 (g, N = 12, each genotype) mg per kg body weight. The latencies to the appearance of sudden immobility, myoclonus and clonic convulsion were shorter in Scn2a^KO/+ than in Scn2a^+/+ mice (Mann-Whitney test, 50 mg per kg, sudden immobility, U = 69.5, ***P = 0.0002, myoclonus, U = 110.5, *P = 0.0145, clonic convulsion, U = 119, *P = 0.0278, tonic-clonic convulsion, U = 188.5, P = 0.7624; 25 mg per kg, sudden immobility, U = 26.5, **P = 0.0071). Data represent means ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001. Scale bars: (a–c) vertical 0.5 mV; horizontal 1 s