In-depth assessment of soticlestat treatment of seizure activity for WT and scn1lab larvae. (A) Swimming behaviour for individual WT (N = 60 across three replicates) and scn1lab (N = 40 across three replicates) larvae after treatment with three concentrations of soticlestat represented as a percent change in velocity from baseline. Increasing concentrations of soticlestat significantly increased velocity of WTs compared to DMSO-treated controls but did not alter the velocity of scn1lab larvae at any concentration. (B) Heatmap showing significant increases in average normalized swimming velocities of soticlestat treated WT larvae compared to scn1lab larvae. (C) Increasing concentrations of soticlestat treatment decreased survival rates of WT larvae but did not impact scn1lab larval survival or responsiveness. (D) LFP recording sample of seizure activity induced in WT larvae after soticlestat treatment along with (E) associated spectrogram. Note the high-frequency activity and electrodecremental LFP response following an ictal-like event. (F) Donut plots representing the percentage of fish showing type 0, 1 and 2 activity for both WT (top, N = 6 across three replicates) and scn1lab (bottom, N = 6 across three replicates) larvae treated with three concentrations of soticlestat with quantification of type 2 events for each seizing fish below each plot. Soticlestat induced type 1 and 2 activity in WT larvae at all concentrations but did not abolish seizure activity in scn1lab larvae unless at high concentrations. Unpaired t-test was performed for statistical analysis, P < 0.05 = *, P < 0.01 = **, P < 0.0001 = **.
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