Figure 8.

R6/2 mice display increased daily activity at the presymptomatic stage. A, Representative single-plotted actogram wheel-running activities of R6/2 mice (n = 17) and littermate wild-type controls (n = 14) are shown. Mice were entrained to 12 h/12 h LD cycles for 9 d (original), followed by a 4 h phase advance of LD cycles for 11 d (phase advance), and were then returned to the original LD cycle for 9 d (phase delay) from 5–9 weeks of age. The white background represents the lightness; the gray background indicates the darkness. B, Times of activity onset in these mice were recorded from day 1 to day 29; the end of phase advance and phase delay were observed at day 14 and day 23, respectively. C, Peaks in the corresponding χ² periodogram for each mouse show a dominant period during 12 h/12 h LD cycles before, during, and after 4 h phase advances. Peaks above the diagonal line (representing the 99.9% confidence level) between 12 and 35 h reflected significant circadian periods. D, Amplitude of circadian rhythms was lower in each LD cycle in R6/2 mice relative to control mice. Bars show the amplitudes at the dominant period, obtained from χ² periodogram analysis. E, Activities in the dark relative to the daily activity of each mouse were averaged before, during, and after 4 h phase advances of the LD cycle. F, Circadian periods (tau) that mice displayed measured in the indicated LD cycles. G, Onset of wheel-running activities, defined as the acrophase, was recorded in the indicated LD cycles. H, Mice at the age of 7 weeks maintained in 12 h/12 h LD cycles were exposed to a single 3 h, 800 lux light pulse at ZT14. The light period is highlighted by the gray dotted box on single-plotted wheel-running activities. The running activities in the light period relative to those in the dark period for each animal were plotted every 10 min from ZT14 to ZT17 (n = 6 for each group). I, Representative double-plotted actograms showing that wheel-running activities of R6/2 (n = 9) and control mice (n = 7) held in a LD cycle until day 10 followed by constant darkness from 7 to 10.5 weeks of age. Mice were exposed to a 15 min 800 lux light pulse (arrow) at CT16 on day 11, followed by a 30 min 300 lux light pulse (double arrows) at CT16 on day 20. J, Changes in the circadian phase due to different intensities of light for the indicated mice. Values are presented as the means ± SEM. **p < 0.01, ***p < 0.001, two-way ANOVA and unpaired t test.