(A) Representative EEG recordings show that a 3-month old Gabrg2+/Q390X knockin mouse had myoclonic jerks (Mj, left panel), interictal discharges (ID, middle panel) which is similar to myoclonic jerks in EEG but without overt behavioral correlation and generalized tonic clonic seizures (GTCS; right panel). (B) The frequency of MJ and ID in the wildtype (wt) or Gabrg2+/Q390X heterozygous (het) mice was measured over a 24-hr session for baseline recording (n=15 for wt and 18 for het, n=15, ****P<0.0001, t=5.429, df=17, One sample t test with test). There was no injection involved in baseline recordings. The total numbers include events with behavioral jerks (MJ) and similar interictal discharges without overt behavioral manifestations (ID). (C) The frequency of behavioral myoclonic jerks in the wt or het mice was measured over the first 15 min of each hour after drug administration. Mice were treated with vehicle (0.9% normal saline, Veh, ip), stiripentol (150mg/kg, STP,ip), diazepam (0.3mg/kg, DZP, ip) alone or a combination of STP and DZP (N=8 for wt vehicle or STP, mice, N=10 for wt DZP, N=7 for STP+DZP; N=11 for het vehicle, STP, DZP and STP+DZP respectively; P<0.0001 for interaction (F(3,69)=22.19; for drug treatment) (F(3,69)=28.07 and for genotype (F(1,69)=73.01)); P<0.001 for both vehicle and STP treated het vs wt, Bonferroni posttests). (D) In pentylenetetrazol (PTZ) treated study, the frequency of total MJ and ID in the wt or het mice was measured over the 15 min after PTZ (50mg/kg, ip) administration (For wt, N=9 mice for vehicle, STP or DZP groups, N=6 mice for STP+DZP; for het, N=8 for vehicle, STP, DZP and STP+DZP respectively, P<0.0001 for interaction (F(3,57)=22.17; drug treatment (F(3,57)=87.17 and genotype (F(1,57)=57.17)); P<0.001 het vs wt for STP+PTZ, Bonferroni posttests. In both C-D, drug treatment and genotype are the independent variables, ***P<0.001 het vs wt with the same drug treated condition; §P<0.05, §§§ P<0.001 vs het vehicle. Two-way ANOVA with Bonferroni posttests. The numbers represent the frequency of events with behavioral jerks and similar interictal discharges without overt behavioral manifestations. (E). Stirpentol alone, as well as in combination with DZP increased survival for Gabrg2+/Q390X knockin mice during pentylenetetrazol (PTZ) seizure induction (N=12–15 for all wildtype and het mice except N=30 mice for het +PTZ group).