Fig. 1: Strong additive effects in double mutant mice on survival, seizure-related behaviors but not ECoG telemetry-recordings.

A Number of mice in litters with experimental time-line. The number of mice was calculated from 12 litters at E18 and 10 litters at age of three weeks (P3w). The number of mice per genotype in genotyped and weaned litters was counted again at the age of 6 weeks, after video monitoring. Exact number of mice per genotype in 12litters (E18) and 10 litters (P3w/P > 6w) is shown in pie-charts. † represents detected sudden unexpected death event in epilepsy (SUDEP). B Video monitoring of single-housed mice revealed different types of behavioral events: generalized seizure, clonic attack, jump, twitch, myoclonus and body extension. The aberrant behavioral events were analyzed in controls (n = 2), Stxbp1 single mutants (n = 5), Snap25 single mutants (n = 4) and double mutants (n = 6). C Average number of twitches and jumps detected in mice during 12 h of video monitoring. D Number of clonic attacks and generalized seizures detected in controls (n = 4), Stxbp1 single mutants (n = 4), Snap25 single mutants (n = 4) and double mutants (n = 7) during 12 h of video monitoring. E Representative ECoG trace of tonic-clonic generalized seizures detected in double mutant mouse with corresponding behavioral state pictogram. F Model of epileptic diversity represents the diversity of epileptic phenotype according to multiplicative model of interaction. We assume that most severe phenotype corresponds to lethal generalized seizures; moderate phenotype corresponds to clonic-tonic seizures and mild phenotype corresponds to low-incidence of SWDs. G 3D representation of different epileptiform events library. Event Classifier application in Neuroarchiver software distinguished three different types of epileptiform activities: SWDs, sharp spikes and spike-slow waves. H-J Number of different epileptiform events during 24 h in controls, Stxbp1 single-, Snap25 single- and double mutants represented as natural logarithm of (number of events +1). H Number of SWDs (I) Number of spike-slow waves and J Number of sharp spikes. K Representation of ECoG traces and corresponding time-frequency spectogram for control, Stxbp1 single-, Snap25 single- and double mutants. L Average relative power during the sleep episodes for all four genotypes. M Quantification of average relative power during the sleep in two frequency bands: delta band (1–4 Hz) and alfa band (9–12 Hz). Shift of relative power to higher frequency bands for all four genotypes is represented as the significant increase of power in alfa frequency band independent on the genotype. Panels represent mean value ± SEM.