Effects of melatonin in group-M: phase shift, entrainment, sleep-promotion and reinstatement of intrinsic rhythm.

<p>Effects of melatonin in group-M: phase shift, entrainment, sleep-promotion and reinstatement of intrinsic rhythm.</p

SCN ablation eliminates intrinsic circadian patterns of activity and food intake in group-M.

<p><b>A</b> & <b>B</b> Double plots of continuous activity recording (left) and corresponding daily profiles (mean value per hour; right panel) of activity (black) and total food intake (red) in M2 before (A) and after (B) electrolytic ablation of the SCN. Black line in A (left plot) highlights the intrinsic free-running rhythm in CDL (τ = 24.3 h), with no such rhythm following the SCN ablation (B). <b>C</b> Similar plots during the period of restricted feeding (RF) in CDL, illustrating entrainment to 24-h period of food availability following SCN lesion. Blue line - onset of food access, black line - end of food access.</p

Similarities between dynamic patterns of spontaneous circadian asynchrony and that following the SCNx in group-M.

<p>The dynamic changes in the power of intrinsic circadian and ultradian rhythms of activity in CDL are reflected in 3D time-by-frequency wavelet maps of a 70-h period of recording for a representative control (<b>A</b>), a group-M animal (M3) with intrinsic circadian asynchrony (<b>B</b>), and a group-M animal (M2) with initially preserved circadian rhythm (<b>C</b>), which was lost following SCN ablation (<b>D</b>). Red arrows point to circadian frequency (∼1 cycle per day). It is continuously present in control and intact M2 (A & C), with ultradian rhythms, especially those with a frequency of more than 6 cycles per day, being prevalent during the active period of subjective day (wavelet ridges: blue-red), and typically low or absent during subjective night (wavelet valleys: purple-black). In contrast, in animals with circadian asynchrony due to familial circadian disorder (B) or SCN ablation (D), the lack of circadian frequency is associated with frequent high-frequency wavelet ridges, which do not follow a circadian pattern. X axis – frequency (cycles per day), Y axis – time (h), Z axis – relative spectral power, reflecting the power of all detected frequencies being 100%, i.e., including those beyond what is shown on the X-axis.</p

The intrinsic rhythms of activity and food intake in group-M under constant dim light conditions.

<p><b>A</b> Left: Stable intrinsic rhythm of activity in monkey M1, with intrinsic circadian period τ = 24.9 h (22 days, shown per Clock Time). Right: corresponding mean patterns of food intake and cognitive performance (mean data profiles, shown per hour of Circadian Time, with CT0 = onset of activity). Red arrow (right panel) - earlier onset of “food through cognitive test” intake, relative to “free-food intake”, reflecting high incidence of incomplete cognitive tests during the day. <b>B,D</b> Power spectrum of activity rhythms within the 0.5–5 cycles per day frequencies (100% = the sum of all the powers shown) for control, M1, M2 and M3. <b>C</b> Raw data recording over 22 days in monkey M3 (shown per Clock Time), illustrating intrinsic asynchrony. Color scheme as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033327#pone-0033327-g001" target="_blank">Fig. 1</a>.</p

Changes in day-night variation in sleep and food intake in Group-M monkeys.

<p><b>A</b> Sleep duration, total (gray), daytime (white) and nighttime (black), in representative Control and Group-M monkey (M1) (as seen in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033327#pone-0033327-g001" target="_blank">Fig. 1A, B</a>) illustrate that increase in total sleep in Group-M is due to delayed awakening and increased sleep during the day, as per extreme eveningness phenotype. <b>B</b> In Group-M animals (shown in M1), the rate of food intake (per hour) is relatively low at daytime (white), when compared to total 24 h (gray) or nighttime (black) rate of their food consumption, or vs. control. In contrast, their nighttime food intake is significantly increased, relative to control. Mean value (SEM) in representative animals; *p<0.01 vs. its own daytime value; # p<0.01 vs. corresponding measure in control.</p

Entrainment to restricted feeding (RF) in control and group-M monkeys.

<p><b>A–C:</b> Continuous recordings in CDL, conducted in parallel over a 50-day period, in a control animal C6 (A), M1 (B) and M3 (C), illustrating free-running during around-the-clock food access in control and M1, and asynchrony in M3 (a), effective entrainment to RF (b), and re-entrainment to a new RF schedule (c). Blue line - onset of food access, black line - end of food access. Dashed green line – depicts an approximate dynamic of anticipatory activity during transition between food access schedules. Color scheme as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033327#pone-0033327-g001" target="_blank">Fig. 1</a>.</p

Persistence of characteristic circadian group-M patterns of activity and food intake in long and short day environment.

<p><b>A</b> & <b>B</b> Long day, 18∶6 LD, in control (<b>A</b>; animal C1, as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033327#pone-0033327-g001" target="_blank">Fig. 1A</a>) and M1 (<b>B</b>). Color scheme as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033327#pone-0033327-g001" target="_blank">Fig. 1</a>. <b>C</b> & <b>D</b> Short day, 6∶18 LD, in control (<b>C</b>, animal C1) and M1 (<b>D</b>). <b>E</b> & <b>F</b> Change in daytime (white) and nighttime (black) food intake (% of total food intake per 24 h) in representative animals (shown in A–D). Mean value (SEM); *p<0.01 vs. its own daytime value; # p<0.01 vs. corresponding measure in control.</p