Seizure phenotype in larval stxbp1b mutant zebrafish. A, Local field potential (LFP) recording from a representative agarose-embedded stxbp1b mutant at 4 d postfertilization (dpf). Electrode is located in the optic tectum. At top is a schematic of the experimental protocol for baseline (0–15 min) and test drug exposure (15–60 min) periods. Test drug in this example is phenytoin (PHT). Type II ictal-like events are denoted by open circles (red). A 60-min continuous gap-free LFP recording trace (top) and associated spectrogram (at bottom) are shown. B, Representative images from age-matched wild-type (WT) sibling and darkly pigmented stxbp1b mutant larvae at 4 dpf. C, Example of a Type II ictal-like event identified using an amplitude threshold detector set to exclude small-amplitude brief interictal-like activity. Note the presence of a brief period of postictal depression in the electrical recording following the event. D, Plot showing the frequency of Type II ictal-like events in stxbp1b mutant larvae used for pharmacology studies (n = 84)

Effect of antiseizure medications (ASMs) on ictal-like seizure events in stxbp1b mutant zebrafish. Individual value plots of ictal event frequency at baseline (0–15 min) and 45–60 min after continuous bath application of a test drug. Independent experiment pairs are indicated by the connected line. A, 1 mM phenytoin (PHT, n = 13); not significant (ns) P = .3364. B, 1 mM valproate (VPA, n = 8); not significant (ns) P = .1274. C, 1 mM ethosuximide (ESX, n = 11); not significant (ns) P = .5364. D, 1 mM levetiracetam (LEV, n = 9); not significant (ns) P = .5337. E, 1 mM diazepam (DZP, n = 12); not significant (ns) P = .5330. Student’s unpaired t tests

Effect of clemizole and trazodone on ictal-like seizure events in stxbp1b mutant zebrafish. A, Individual value plot of ictal event frequency at baseline (0–15 min) and 45–60 min after continuous bath application of 1 mM clemizole (CLM, n = 11). Independent experiment pairs are indicated by the connected line. ***P < .0001. B, Representative 60-min local field potential (LFP) traces for stxbp1b mutant zebrafish at baseline (6.5 ± 0.6 events/15 min) and 45–60 min after clemizole exposure (1.3 ± 0.3 events/15 min). Ictal events are noted by open red circles above traces. C, Individual value plot of ictal event frequency at baseline (0–15 min) and 45–60 min after continuous bath application of 1 mM trazodone (TRZ, n = 14). Independent experiment pairs are indicated by the connected line. ***P < .0001. D, Representative 60-min LFP traces for stxbp1b mutant zebrafish at baseline (8.2 ± 1.4 events/15 min) and 45–60 min after trazodone exposure (1.4 ± 0.4 events/15 min). Ictal events are noted by open red circles above traces. Student’s unpaired t tests