Figure 1.
Disintegration of daily rhythm of activity in R6/2 mice.
Double-plotted actograms from representative WT (A) and R6/2 (B) mice measured under LD conditions (12 h:12 h). Light/dark activity ratio (C), onset of activity (D), and acrophase (E) were averaged across 7 days. Open symbols are WT mice, filled symbols are R6/2 mice. Data are means ± SEM. *** = p<0.001.
Figure 2.
Amplitude of the daily activity cycle, averaged over every 7 day period.
Results are shown from mice being kept under constant LD conditions (A), subjected to repeated phase shifts (B), and following jet-lag phase-advance (C) and phase-delay (D). WT mice are shown as open symbols. R6/2 mice are represented by filled symbols. Data are means ± SEM. * = p<0.05, ** = p<0.01, *** = p<0.001.
Figure 3.
Double-plotted actograms from mice subjected to repeated 4 hour phase-advances (shaded blocks).
Representative WT mice are shown in (A), and R6/2 mice in (B). Phase angles of entrainment throughout the study are shown in C. The dotted lines in C indicate linear regression in R6/2 mouse data from 8–14 weeks, and 14.5–17 weeks. Inter-genotype comparisons of angles of entrainment from the second week of each phase-advance are shown in D. E shows intra-genotype comparison of phase angles from the second week of each phase-advance. F shows the light/dark (LD) activity ratios under normal 12∶12 LD conditions (squares) and following repeated phase-advance (circles). G shows average acrophase for the second week following each phase-advance. In C-G, WT mice are shown as open symbols/columns, R6/2 mice are represented by filled symbols/columns. Data in C-G are means ± SEM. * = p<0.05, ** = p<0.01, *** = p<0.001.
Figure 4.
Average time of onset of activity of mice subjected to repeated phase-shifts, showing time to PS50 (the time at which half of the phase-shift was achieved).
Light phase-shifts were conducted between 8–10 (A), 10–12 (B), 12–14 (C) and 14–15 (D) weeks of age. All values are means ± SEM. Open symbols are WT mice, filled symbols are R6/2 mice.
Table 1.
Inter-genotype comparison of number of days taken to reach PS50 in the serial phase-advance experiment, analyzed using raw data.
Table 2.
Inter-genotype comparison of number of days taken to reach PS50 in the serial phase-advance experiment, analyzed using zeroed data.
Figure 5.
Representative double plotted actograms from mice undergoing phase-advance and phase-delay.
WT (A, B) and R6/2 (C, D) mice were exposed to either phase-advance (A and C) or phase-delay (B and D). Shaded regions represent dark phase of LD cycle. Lines were drawn to plot onsets of activity for each mouse (as shown for representative mice in A-D). Lines from all mice are shown superimposed in E and F.
Figure 6.
Periodograms from the second week of each phase-shift in the shift/reversal experiment from representative WT and R6/2 mice.
Panel A shows a WT mouse undergoing phase-delay and reversal, Panel C an R6/2 mouse under the same conditions. Panel B shows a WT mouse undergoing phase-advance and reversal, Panel D an R6/2 mouse under the same conditions. The amplitude decreased with age in R6/2 mice, but was more strongly maintained under conditions of phase-delay with phase-advance as the reversal, than under phase-advance with phase-delay as the reversal. The dotted line in the periodograms represents significance at p<0.001.
Figure 7.
Acrophase and light/dark ratios in the shift/reversal experiment.
Acrophase (A and B) and light/dark ratios (C and D) for WT (open columns) and R6/2 (filled columns) mice are shown following both phase-advance (A, C) and phase-delay (B, D). Data in A and B are means ± SEM of the acrophase in each week of the experiment. Data in C and D are the light/dark ratios from the second 7 days of each cycle. * = p<0.05, ** = p<0.01, *** = p<0.001.
Figure 8.
Phase angles of entrainment in the shift/reversal experiment.
Mice were kept under normal LD conditions until 15 weeks of age, and were then subjected to two weeks of phase-advance followed by reversal to normal LD conditions (A), or to two weeks of phase-delay followed by reversal (B). Dotted lines indicate the start of each phase-shift. Open symbols are WT mice, filled symbols are R6/2 mice. Data are means ± SEM. * = p<0.05, ** = p<0.01, *** = p<0.001.
Figure 9.
Average time of onset of activity of mice subjected to phase-shift/reversals, showing time to PS50 (the time at which half of the phase-shift was achieved).
Mice were subjected to either a 6 hour phase-advance (A) followed by a 6 hour reversal (B), or a 6 hour phase-delay (C) again followed by a 6 hour reversal (D). Data are means ± SEM. Open symbols are WT mice, filled symbols are R6/2 mice.
Table 3.
Intra- and inter- genotype comparison of number of days to PS50 in the shift/reversal experiment.
Figure 10.
Activity in mice kept under a 23 hour LD cycle.
Double-plotted actograms from representative WT (A) and R6/2 (B) mice. Each circadian cycle is 23 hours long, so every line of the double-plotted actograms represents 46 hours. Light/dark activity ratio (C), onset of activity (D), and acrophase (E) were averaged across 7 days. Open symbols are WT mice, filled symbols are R6/2 mice. Data are means ± SEM. * = p<0.05, *** = p<0.001.
Figure 11.
Survival data from R6/2 mice in the shift/reversal experiment.
There was no overall effect of experimental condition on survival. However, in the phase-advance group (filled symbols), the first 50% of mice died significantly sooner than those in the phase-delay group (open symbols).