Figure 6. Stxbp1^tm1d/+ mice exhibit cortical hyperexcitability and epileptic seizures.

(A–D) Representative EEG traces of the left frontal cortex (L-FC), left somatosensory cortex (L-SC), and right somatosensory cortex (R-SC), and EMG traces of the neck muscle from WT (A,B) and Stxbp1^tm1d/+ mice (C,D). Spike-wave discharges (SWDs, indicated by the blue arrows) occurred frequently and often in a cluster manner in Stxbp1^tm1d/+ mice (see Video 1). The gray line-highlighted SWDs from WT and Stxbp1^tm1d/+ mice were expanded to show the details of the oscillations (B,C). A long SWD (i.e.,>4 s) during REM sleep from a Stxbp1^tm1d/+ mouse is shown in (D) (see Video 2). (E) Summary data showing the overall SWD frequency (left panel), duration (middle panel), and average spike rate (right panel). (F) The numbers of SWDs per hour in WT (left Y axis) and Stxbp1^tm1d/+ (right Y axis) mice are plotted as a function of time of day and averaged over 3 days. (G) Video frames showing a myoclonic jump from a Stxbp1^tm1d/+ mouse (see Video 3). The mouse was in REM sleep before the jump. (H) Representative EEG and EMG traces showing myoclonic jerks (indicated by the blue arrows) from a Stxbp1^tm1d/+ mouse (see Video 4). Two episodes of myoclonic jerks highlighted by the gray lines were expanded to show that the EEG discharges occurred prior to (the first episode) or simultaneously with (the second episode) the EMG discharges. (I,J) Summary data showing the frequencies of two types of myoclonic seizures in different behavioral states. The numbers and ages of recorded mice are indicated in the figures. Each filled (male) or open (female) circle represents one mouse. Bar graphs are mean ± s.e.m. n.s., p>0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001.

Figure 6—figure supplement 1. The clustering of SWDs in Stxbp1^tm1d/+ mice does not result from a random distribution of frequent SWD episodes.

(A–C) In Stxbp1^tm1d/+ mice, many SWDs occurred in a cluster manner. A SWD cluster is defined as five or more episodes of SWDs that occur with an inter-episode-interval of 60 s or less. For each Stxbp1^tm1d/+ mouse, simulations were performed to determine if the clustering of SWD episodes was simply due to the overall high frequencies of episodes. The recorded episodes of SWDs from a Stxbp1^tm1d/+ mouse were randomly distributed in the same period of time for 10⁶ times. The number of SWD clusters was determined from each simulated distribution, and the results of the 10⁶ simulations are shown as the probability distribution of the number of SWD clusters for each mouse. The vertical lines with the same color as the probability distribution curves represent the numbers of the recorded SWD clusters in each mouse. The numbers of simulated SWD clusters are all smaller than that of recorded SWD clusters for each Stxbp1^tm1d/+ mouse (p<10⁻⁶), demonstrating that a random distribution of the same number of SWD episodes does not result in the same clustering of SWDs in Stxbp1^tm1d/+ mice.