Fig. 1. Differential ECoG recordings from electrodes implanted in the front parietal cortex in C3H mice. Top: Baseline ECoG activity (top) in control littermates (n = 4). Bottom: Baseline with recurrent bilaterally synchronous 350- to-450-μV intermittent 5- to 6-Hz spike-and-wave discharges recorded in AY-9944 treated mice (n = 4). No behavioral arrest was associated with the epileptiform discharges in AY-treated mice. Calibration: 100 μV/5 seconds scale. F, frontal electrodes; P, parietal electrodes.

Fig. 2. Daily rhythm in the duration of 5- to 6-Hz slow spike-and-wave discharges (SSWDs) in AY-treated rats. The dashed line represents the underlying oscillation at a frequency of 1 cycle per day (i.e., single-oscillator model). The mesor was 94.33 ± 2.68 seconds, with an amplitude of 22.78 ± 3.81 seconds and peak duration occurring at 1913 hours local time. However, the SSWD rhythm exhibited multiple peaks and nadirs within the 24-hour day, a profile indicative of an ultradian rhythm, and thus fit well (R² = 0.55) a two-oscillator model. The second oscillator had an amplitude of 8.89 ± 4.72 seconds, with its first peak at 1929 hours and subsequent peaks occurring every 11 hours 46 minutes. cpd, cycles per day.

Fig. 3. Behavioral activity levels in AY-treated mice during the light phase and dark phase. Long-term behavioral recordings revealed that AY-treated mice were hyperactive compared with controls. The AY group exhibited significantly higher TM (A), MT (B), AMT (C), JFP (F), and TURNS (G) during both phases of the photocycle. There was no between-group difference in light-phase CT (D). Within-group comparisons of light-phase and dark-phase means indicated that AY-treated mice were more active during the dark phase, with significantly higher TM (A), CT (D), JFP (F), and TURNS (G). Similar within-group comparisons for control mice indicated that TM was significantly higher during the dark phase (A) only, though STPY (E) had approached significance. TM, total movements; MT, movement time; CT, center time; JFP, jumps; TURNS; rotations; AMT, ambulatory movement time; STPY, percentage stereotypy.

Fig. 4. Daily rhythm of behavioral activity in AY-treated mice. Dashed lines represent the underlying oscillation of total behavioral activity in AY-treated (black) and control (gray) mice at a frequency of 1 cycle per day (i.e., single-oscillator model). The AY-treated mice exhibited a significantly higher mesor than controls, with an activity profile that was significantly elevated during both phases of the light–dark cycle. There was no difference in rhythm amplitude between the groups. In AY-treated and control mice, higher TM were confined to the dark phase, with peaks at 0207 and 0132 hours, respectively.

Analysis of the daily rhythms of SSWD duration and TM in the AY seizure model

Note. All data presented as the mean ± SEM. Phase data presented as hours from subjective midnight with the corresponding clock time in parentheses. SSWD, slow spike–wave discharge; TM, total movement; NS, not significant; hfm, hours from subjective midnight; R², coefficient of determination.

^2cpd Cosinor fit using two-oscillator model.

^AP Level of significance for one-way ANOVA for TM only (down column).