Nocturnal rodents show diurnal food anticipatory activity when food access is restricted to a few hours in daytime. Timed food access also results in reduced food intake, but the role of food intake in circadian organization per se has not been described. By simulating natural food shortage in mice that work for food we show that reduced food intake alone shifts the activity phase from the night into the day and eventually causes nocturnal torpor (natural hypothermia). Release into continuous darkness with ad libitum food, elicits immediate reversal of activity to the previous nocturnal phase, indicating that the classical circadian pacemaker maintained its phase to the light-dark cycle. This flexibility in behavioral timing would allow mice to exploit the diurnal temporal niche while minimizing energy expenditure under poor feeding conditions in nature. This study reveals an intimate link between metabolism and mammalian circadian organization.
Citation: Hut RA, Pilorz V, Boerema AS, Strijkstra AM, Daan S (2011) Working for Food Shifts Nocturnal Mouse Activity into the Day. PLoS ONE 6(3): e17527. https://doi.org/10.1371/journal.pone.0017527
Editor: Shin Yamazaki, Vanderbilt University, United States of America
Received: December 9, 2010; Accepted: February 3, 2011; Published: March 30, 2011
Copyright: © 2011 Hut, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was supported by EC-FP6 Integrated Project 018741 "EUCLOCK", EMBO fellowship 666828 to RAH, and EC-FP6 Marie-Curie fellowship 221095 "ClockWork" to VP (project supervisor RAH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Mice and rats are nocturnal, but their activity shifts to the day when food access is restricted to a few hours in daytime. In such restricted schedules the food received is limited both in time and in quantity (typically 60–70% of normal daily food intake). This procedure induces food anticipatory activity (FAA) a few hours before the food is delivered . FAA is thought to be the behavioral output of a separate circadian oscillator called the food entrainable oscillator (FEO) which is entrained by periodic food availability and capable of driving peripheral ,  and behavioral rhythms . Under these conditions the FEO drives the activity rhythm independently of the suprachiasmatic nucleus (SCN), which controls nocturnal activity under standard ad libitum conditions , . The anatomical substrate of the FEO remains elusive in spite of intense investigation and debate , –.
In nature, food availability is hardly periodic to most rodents, and diurnal activity has often been observed in nocturnal animals –. A crucial difference between lab and field is that animals in the field have to work (i.e. spend time and energy) to obtain food. To study the effect of reduced food intake on circadian organization, we simulated natural food scarcity by having mice work for their food at increasing levels of workload under a 12 h light - 12 h dark (LD) cycle, without restricting food access to a specific time of day.
Reducing food reward per unit workload (i.e. wheel running in mammals or perch hopping in birds) reduced daily food intake (Fig. 1C) as described in other species . As a result mice spontaneously shifted their activity to the light phase of the day (Fig. 1A–B). This procedure increased activity in daytime while total activity per 24 h remained stable or was slightly reduced (Fig. 1D). Detailed comparison of activity onsets and offsets during the last 8 days in LD and the first 8 days in DD shows that low reward ratios advance activity onsets by 5.5 h (paired T-test, p<0.0001) and offsets by 4.6 h (paired T-test, p = 0.0003) relative to the estimated phase of the main circadian pacemaker during entrainment (as extrapolation from activity patterns after release in DD with ad libitum food; Fig.1E red vs. green bars). Control mice on ad libitum food access throughout the experiment did not show advanced activity onsets in LD but rather delayed offsets (paired T-test: onsets, 0.8 h advanced, p = 0.08; offsets, 2.7 h delayed p = 0.01; Fig.1E grey bars). Low reward ratio advanced activity onsets in LD by 6.4 h (p<0.0001) and offsets by 9.7 h (p<0.0001) when compared to control mice (Fig.1E, red vs. top grey bar). After release in DD and ad libitum food conditions, the estimated phase of the circadian pacemaker during entrainment was 1.7 h (p = 0.0004) advanced for the onset of activity and 2.4 h advanced for the offset of activity (green vs. grey bar) when compared to the ad libitum control mice. Taken together, these data indicate that reduced food intake shifts activity from the dark phase into the light phase. Upon release into DD with food available ad libitum, activity patterns instantaneously reverted to the previous dark phase (Fig. 1A, B). This may suggest that the circadian pacemaker had remained entrained to the LD cycle, albeit with a slightly advanced phase relative to that of mice kept on ad libitum food supply throughout the experiment (Fig. 1E).
(A, B) Two example actograms show the gradual shift from nocturnal to diurnal wheel running. (C) Gradual reward ratio reduction (grey bars) reduces total food obtained (line, in g/d; thin lines indicate s.e.m.). (D) Total activity per 24 h was slightly reduced but shifted largely to the day when the reward ratio was reduced (red compared to blue and cyan). The immediate shift to the previous dark phase after release in DD with ad libitum food indicates normal entrainment of the circadian pacemaker to the previous LD cycle (A, B; days 59–66). (E) Average activity onsets and offsets for working mice during the last 8 days under LD (red bar) and first 8 days in DD (green bar), and for the ad libitum control mice (grey bars) during the same time intervals.
Daily rhythms in core body temperature (Tb) were associated with activity both in mice that work for their food and in ad libitum fed mice (Fig. 2). High Tb episodes gradually shifted to the light phase when reward ratio was reduced in mice working for food (Fig. 2A–B), but remained in the dark phase in control mice (Fig. 2C). While resting Tb rarely approached 30°C in control mice, mice under low reward ratio gradually reduced resting Tb, eventually resulting in daily torpor well below 30°C (Fig. 2, Fig. S1) . In some mice activity shifted to the light phase well before torpor occurred (Fig. S2), indicating that the behavioral shift is not caused by the occurrence of torpor (Fig. 2B).
(A, B) Two example actograms and body temperature patterns of mice under a reduced reward ratio protocol (grey bars) and (C) a control mouse kept under ad libitum conditions. Low daily food rewards (side panels, black lines) eventually elicited torpor response (blue colors) after activity patterns shifted to the light (see also Fig. S3). No evidence of torpor was found in any of the control mice. Black and white bars indicate the light-dark cycle to which the mice were exposed throughout the experiment.
Unlike control mice that show lowest Tb always during the light phase, lowest Tb in mice with a low reward ratio occurred in the last part of the night (Fig. 2A–B). The timing of torpor would thus coincide with the coldest phase of the daily cycle under natural conditions. This may have functional significance since at that time of day burrow retreat and torpor will have larger energetic benefits.
To test whether the shift in activity patterns from nocturnal to diurnal depends on the presence of a light dark cycle, we applied the work for food protocol in mice kept under continuous dim red light (DD, Fig. 3A–D). Here we identified a main activity component (Actmain), which seems unaffected by the work for food protocol, and a less intense activity component (Actshifted) that followed the main activity component under high reward ratio and ad libitum conditions. Actshifted component shifted and preceded the main activity component under medium and low reward ratio conditions (Fig. 3D). When mice under low reward ratio conditions were fed ad libitum, the preceding Actshifted component immediately shifted back to its normal phase position and followed Actmain. This observation is paralleled by the immediate return from diurnal to nocturnal activity patterns when working mice in an LD cycle were placed on ad libitum food access (Fig. 1. A–B).
(A, B) Two examples of free-running activity rhythms in mice that work for food are shown in double plotted actogram format. (C) Gradual reward ratio reduction (grey bars) and food obtained (line, in g/d; thin lines indicate s.e.m.) shifted circadian activity patterns. (D) Graphical interpretation of observed activity patterns where a shifted activity component (Actshifted, light grey area) is discerned from a non-shifted main activity component (Actmain, dark grey area). Four different work levels were applied: high reward ratio (C, blue bar), medium reward ratio (C, purple bar), low reward ratio (C, red bar), and ad libitum (C, green bar).
Our data indicate that the output of the SCN driving activity cycles is modified downstream. Since the activity pattern gradually shifts towards diurnality when energy intake is reduced (Fig. 1A–B; 2A–B), it is plausible that this activity pattern is controlled by a slave oscillator that changes its phase position with respect to the SCN.
Activity-rest oscillators outside the SCN have been demonstrated both in temporally restricted fed animals (FEO ) and in rodents given access to low concentrations of methamphetamine in the drinking water (methamphetamine sensitive circadian oscillator, MASCO , . The FEO, the MASCO, and the activity regulating oscillator presented here are all expressed under modified metabolic conditions. They may very well turn out to rely on the same physiological mechanism and anatomical structure.
Reduced reward ratios in mice that run their wheel to obtain food resemble natural conditions, where travelling distance between food patches increases when food becomes scarce . Our data may reveal the strategy that mice adopt to cope with reduced energy intake under natural conditions. Two alternative strategies to maintain energy balance under such conditions can be hypothesized (Fig. 4): A) foraging activity time per day remains constant and mice reduce energy expenditure during rest to match reduced energy intake; B) resting metabolic rate remains constant and mice increase foraging time per day to balance daily intake and expenditure. Both strategies were quantified and graphically represented (Fig. 4) using measures of energy expenditure from previous work (see Text S1 – Model Calculations). Although one might expect a combination of these strategies, the normal activity levels (Fig. 1) and the reduction in body temperature (Fig. 2) indicates that CBA/CaJ mice that work for food follow strategy A to maintain their energy balance when energy intake is reduced.
Using known values for energy expenditure during rest and activity (see Text S1 - Model Calculations) we illustrate how mice may cope with reduced energy intake either by (A) reducing resting metabolic rate while duration of daily foraging activity remains constant (strategy A), or by (B) expanding daily foraging while metabolic rates during rest and activity remain constant (strategy B). With decreasing daily energy intake during activity, strategy A predicts a gradual reduction in body temperature during the rest phase, and reduced daily energy expenditure (DEE), while strategy B leads to a gradual increase in activity duration and DEE. Both strategies reach a limit when net energy intake during foraging drops below ∼1.4 Watts.
These results provide novel insight to the current debate on the FEO, in which mice show diurnal (food anticipatory) activity when feeding is restricted during a few hours in the light phase. This restricted diurnal meal timing is thought to uncouple activity rhythms from the circadian pacemaker (SCN) signal , . The timed food restriction protocol used to study entrainment of the FEO carries the confounding risk that two variables are manipulated simultaneously: meal timing and reduced food intake (∼70–75% for 3 h food access in mice; ). Mendoza et al.  showed that diurnal activity occurs also when 6 short meals are presented at 4 h intervals, a procedure which still involves imposed meal timing. Mice in the present study chose themselves when to work for their food, indicating that reduced food intake alone, and not meal timing, was crucial to the occurrence of diurnal activity. Diurnal activity patterns in house mice were recently observed to persist for months under semi-natural conditions with competition for food access . This diurnal behavior would allow mice to forage during the warmer part of the day and to time rest and hypothermia (torpor) at the end of the night. This temporal niche switching would minimize daily energy expenditure, possibly at the cost of increased predation risk during the day. The ‘work for food’ paradigm presented here reveals adaptive flexibility in circadian organization and a strong link between metabolism and the circadian system in an intact mammal. It avoids possible confounding effects of food timing and rationing, that are inherent to the classical food entrainment protocol. Spontaneous diurnal activity elicited in mice that work for food may open new approaches to describe an alternative circadian activity-rest oscillator, and will lead to a better understanding of temporal organization of behavior under natural conditions.
All animal experiments were approved by the University of Groningen ethical committee (DEC 5011, 5114, 5454) and carried out following (inter-) national animal welfare regulations.
Adult male mice (CBA/CaJ; Jackson Laboratory, Bar Harbor, Maine, USA) were kept under standard laboratory conditions (see Text S1 – Detailed Methods). Sample sizes were as follows: Fig. 1&2: control n = 12, experimental n = 12; Fig. 3: n = 12. Running wheel activity was recorded continuously and stored in 2-min bins. Onsets and offsets of activity (Fig. 1E) were determined over 8 days just before the switch to DD or right after the switch to DD following the procedure previously described . In the work for food protocol, a small 45 mg food pellet (F0165; Bio-Serv, Frenchtown NJ, USA) was delivered in the mouse cage after a set number of wheel revolutions using computer controlled pellet dispensers (Med Associates Inc., St.Albans VT, USA). During the ‘work for food’ protocol, mice started on a high reward schedule (100 revolutions/pellet). This generated essentially an ad libitum food condition, because excess pellets were observed in each individual kept under these conditions. During the reward reduction phases of the experiment, workload was increased daily by an extra 10–20 revolutions per pellet up to 200 revolutions per pellet (medium reward schedule) or 300–400 revolutions per pellet (low reward schedule). Throughout the experiment body mass was closely monitored at least every 3rd day at different times of day and high workload levels were individually titrated to keep the mice above 18 grams and 75% of their initial body mass.
Body temperature was measured by customised temperature loggers (Thermochron iButton, DS1922L, Maxim Integrated Products Inc., Sunnyvale CA, USA) implanted in the abdominal cavity of the mice and set to a sampling rate of once every 20 minutes (see Text S1 – Detailed Methods).
Supporting Information for ‘Working for food shifts nocturnal mouse activity into the day’.
Reduced food reward affects body temperature patterns. Body temperature patterns of two representative animals with gradually reduced food reward (A, B) and an ad libitum control animal (C). Body temperature occurring during the rest phase is reduced, eventually leading to torpor. Data are from the same animals as presented in Fig. 1 (panel identifiers correspond).
Reduced food reward shifts activity rhythms before torpor occurs. This example shows that some animals in the experiment presented in Fig. 2 and Fig. S1 clearly showed a shifted activity rhythm well before torpor occurs. The opposite (torpor occurs before the activity rhythm is shifted) was never observed. These data indicate that torpor is not necessary to shift the activity rhythms into the day. It is rather the shifted activity rhythms that allow torpor to occur in the dark phase.
We thank M. Menaker and M. Sellix for critically reading the manuscript, M. Huizinga and C. Reizema-Klein for excellent animal care, M.M.T. van der Pol for operation assistance, and G.J.F. Overkamp for technical assistance.
Conceived and designed the experiments: RAH VP. Performed the experiments: VP RAH. Analyzed the data: VP RAH. Wrote the paper: RAH VP SD. Performed pilot studies: ASB AMS. Performed model calculations: SD.
- 1. Mistlberger RE (2009) Food-anticipatory circadian rhythms: concepts and methods. Eur J Neurosci 30: 1718–1729.RE Mistlberger2009Food-anticipatory circadian rhythms: concepts and methods.Eur J Neurosci3017181729
- 2. Pezuk P, Mohawk JA, Yoshikawa T, Sellix MT, Menaker M (2010) Circadian Organization Is Governed by Extra-SCN Pacemakers. J Biol Rhythms 25: 432–441.P. PezukJA MohawkT. YoshikawaMT SellixM. Menaker2010Circadian Organization Is Governed by Extra-SCN Pacemakers.J Biol Rhythms25432441
- 3. Stokkan KA, Yamazaki S, Tei H, Sakaki Y, Menaker M (2001) Entrainment of the circadian clock in the liver by feeding. Science 291: 490–493.KA StokkanS. YamazakiH. TeiY. SakakiM. Menaker2001Entrainment of the circadian clock in the liver by feeding.Science291490493
- 4. Stephan FK (2001) Food-entrainable oscillators in mammals. In: Takahashi JS, Turek FW, Moore RY, editors. (New York: Kluwer Academic/Plenum Publishers). pp. 223–246.FK Stephan2001Food-entrainable oscillators in mammals.JS TakahashiFW TurekRY Moore(New YorkKluwer Academic/Plenum Publishers)223246In Circadian Clocks. In Circadian Clocks.
- 5. Ralph MR, Foster RG, Davis FC, Menaker M (1990) Transplanted suprachiasmatic nucleus determines circadian period. Science 247: 975–978.MR RalphRG FosterFC DavisM. Menaker1990Transplanted suprachiasmatic nucleus determines circadian period.Science247975978
- 6. Kawamura H, Inouye ST (1979) Circadian rhythm in a hypothalamic island containing the suprachiasmatic nucleus. In: Suda M, Hayaishi O, Nakagawa H, editors. In Biological rhythms and their central mechanism. (Amsterdam: Elsevier). pp. 335–341.H. KawamuraST Inouye1979Circadian rhythm in a hypothalamic island containing the suprachiasmatic nucleus.M. SudaO. HayaishiH. NakagawaIn Biological rhythms and their central mechanism(AmsterdamElsevier)335341
- 7. Davidson AJ (2009) Lesion studies targeting food-anticipatory activity. Eur J Neurosci 30: 1658–1664.AJ Davidson2009Lesion studies targeting food-anticipatory activity.Eur J Neurosci3016581664
- 8. Moriya T, Aida R, Kudo T, Akiyama M, Doi M, Hayasaka N, Nakahata N, Mistlberger , Okamura H, Shibata S (2009) The dorsomedial hypothalamic nucleus is not necessary for food-anticipatory circadian rhythms of behavior, temperature or clock gene expression in mice. Eur J Neurosci 29: 1447–1460.T. MoriyaR. AidaT. KudoM. AkiyamaM. DoiN. HayasakaN. NakahataMistlbergerH. OkamuraS. Shibata2009The dorsomedial hypothalamic nucleus is not necessary for food-anticipatory circadian rhythms of behavior, temperature or clock gene expression in mice.Eur J Neurosci2914471460
- 9. Mistlberger RE, Rechtschaffen A (1984) Recovery of anticipatory activity to restricted feeding in rats with ventromedial hypothalamic lesions. Physiol Behav 33: 227–235.RE MistlbergerA. Rechtschaffen1984Recovery of anticipatory activity to restricted feeding in rats with ventromedial hypothalamic lesions.Physiol Behav33227235
- 10. Feillet CA, Mendoza J, Albrecht U, Pevet P, Challet E (2008) Forebrain oscillators ticking with different clock hands. Mol Cell Neurosci 37: 209–221.CA FeilletJ. MendozaU. AlbrechtP. PevetE. Challet2008Forebrain oscillators ticking with different clock hands.Mol Cell Neurosci37209221
- 11. Challet E, Bernard DJ, Turek FW (1998) Lesions of glucose-responsive neurons impair synchronizing effects of calorie restriction in mice. Brain Res 801: 244–250.E. ChalletDJ BernardFW Turek1998Lesions of glucose-responsive neurons impair synchronizing effects of calorie restriction in mice.Brain Res801244250
- 12. Challet E, Pevet P, Lakhdar-Ghazal N, Malan A (1997) Ventromedial nuclei of the hypothalamus are involved in the phase advance of temperature and activity rhythms in food-restricted rats fed during daytime. Brain Res Bull 43: 209–218.E. ChalletP. PevetN. Lakhdar-GhazalA. Malan1997Ventromedial nuclei of the hypothalamus are involved in the phase advance of temperature and activity rhythms in food-restricted rats fed during daytime.Brain Res Bull43209218
- 13. Challet E, Le MY, Pevet P, Nobelis P, Malan A (1996) Ventromedial hypothalamic lesions prevent the fasting-induced changes in day-night pattern of locomotor activity. Behav Brain Res 77: 155–163.E. ChalletMY LeP. PevetP. NobelisA. Malan1996Ventromedial hypothalamic lesions prevent the fasting-induced changes in day-night pattern of locomotor activity.Behav Brain Res77155163
- 14. Challet E, Pévet P, Malan A (1996) Intergeniculate leaflet lesion and daily rhythms in food-restricted rats fed during daytime. Neurosci Lett 216: 214–218.E. ChalletP. PévetA. Malan1996Intergeniculate leaflet lesion and daily rhythms in food-restricted rats fed during daytime.Neurosci Lett216214218
- 15. Mieda M, Williams SC, Richardson JA, Tanaka K, Yanagisawa M (2006) The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker. Proc Natl Acad Sci USA 103: 12150–12155.M. MiedaSC WilliamsJA RichardsonK. TanakaM. Yanagisawa2006The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker.Proc Natl Acad Sci USA1031215012155
- 16. Krieger DT, Hauser H, Krey LC (1977) Suprachiasmatic nuclear lesions do not abolish food-shifted circadian adrenal and temperature rhythmicity. Science 197: 398–399.DT KriegerH. HauserLC Krey1977Suprachiasmatic nuclear lesions do not abolish food-shifted circadian adrenal and temperature rhythmicity.Science197398399
- 17. Gooley JJ, Schomer A, Saper CB (2006) The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms. Nat Neurosci 9: 398–407.JJ GooleyA. SchomerCB Saper2006The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms.Nat Neurosci9398407
- 18. Landry GJ, Yamakawa GR, Webb IC, Mear RJ, Mistlberger RE (2007) The dorsomedial hypothalamic nucleus is not necessary for the expression of circadian food-anticipatory activity in rats. J Biol Rhythms 22: 467–478.GJ LandryGR YamakawaIC WebbRJ MearRE Mistlberger2007The dorsomedial hypothalamic nucleus is not necessary for the expression of circadian food-anticipatory activity in rats.J Biol Rhythms22467478
- 19. Landry GJ, Simon MM, Webb IC, Mistlberger RE (2006) Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats. Am J Physiol Regul Integr Comp Physiol 290: R1527–R1534.GJ LandryMM SimonIC WebbRE Mistlberger2006Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats.Am J Physiol Regul Integr Comp Physiol290R1527R1534
- 20. Storch KF, Weitz CJ (2009) Daily rhythms of food-anticipatory behavioral activity do not require the known circadian clock. Proc Natl Acad Sci USA 106: 6808–6813.KF StorchCJ Weitz2009Daily rhythms of food-anticipatory behavioral activity do not require the known circadian clock.Proc Natl Acad Sci USA10668086813
- 21. Pendergast JS, Nakamura W, Friday RC, Hatanaka F, Takumi T, Yamazaki S (2009) Robust food anticipatory activity in BMAL1-deficient mice. PLoS ONE 4: e4860.JS PendergastW. NakamuraRC FridayF. HatanakaT. TakumiS. Yamazaki2009Robust food anticipatory activity in BMAL1-deficient mice.PLoS ONE4e4860
- 22. Landry GJ, Mistlberger RE (2007) Food entrainment: methodological issues. J Biol Rhythms 22: 484–487.GJ LandryRE Mistlberger2007Food entrainment: methodological issues.J Biol Rhythms22484487
- 23. Mistlberger RE, Buijs RM, Challet E, Escobar C, Landry GJ, Kalsbeek A, Pevet P, Shibata S (2009) Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- mice. J Circadian Rhythms 7: 3.RE MistlbergerRM BuijsE. ChalletC. EscobarGJ LandryA. KalsbeekP. PevetS. Shibata2009Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- mice.J Circadian Rhythms73
- 24. Hoogenboom I, Daan S, Dallinga H, Schoenmakers M (1984) Seasonal change in daily timing of behaviour in the common vole Microtus arvalis. Oecologia 61: 18–31.I. HoogenboomS. DaanH. DallingaM. Schoenmakers1984Seasonal change in daily timing of behaviour in the common vole Microtus arvalis.Oecologia611831
- 25. Levy O, Dayan T, Kronfeld-Schor N (2007) The relationship between the golden spiny mouse circadian system and its diurnal activity: an experimental field enclosures and laboratory study. Chronobiol Int 24: 599–613.O. LevyT. DayanN. Kronfeld-Schor2007The relationship between the golden spiny mouse circadian system and its diurnal activity: an experimental field enclosures and laboratory study.Chronobiol Int24599613
- 26. Gattermann R, Johnston RE, Yigit N, Fritzsche P, Larimer S, Ozkurt S, Neumann K, Song Z, Colak E, Johnston J, McPhee ME (2008) Golden hamsters are nocturnal in captivity but diurnal in nature. Biol Lett 4: 253–255.R. GattermannRE JohnstonN. YigitP. FritzscheS. LarimerS. OzkurtK. NeumannZ. SongE. ColakJ. JohnstonME McPhee2008Golden hamsters are nocturnal in captivity but diurnal in nature.Biol Lett4253255
- 27. Spoelstra K, Albrecht U, van der Horst GT, Brauer V, Daan S (2004) Phase responses to light pulses in mice lacking functional per or cry genes. J Biol Rhythms 19: 518–529.K. SpoelstraU. AlbrechtGT van der HorstV. BrauerS. Daan2004Phase responses to light pulses in mice lacking functional per or cry genes.J Biol Rhythms19518529
- 28. Wiersma P, Verhulst S (2005) Effects of intake rate on energy expenditure, somatic repair and reproduction of zebra finches. J Exp Biol 208: 4091–4098.P. WiersmaS. Verhulst2005Effects of intake rate on energy expenditure, somatic repair and reproduction of zebra finches.J Exp Biol20840914098
- 29. Schubert KA, Boerema AS, Vaanholt LM, de Boer SF, Strijkstra AM, Daan S (2009) Daily torpor in mice: high foraging costs trigger energy-saving hypothermia. Biol Lett 6: 132–135.KA SchubertAS BoeremaLM VaanholtSF de BoerAM StrijkstraS. Daan2009Daily torpor in mice: high foraging costs trigger energy-saving hypothermia.Biol Lett6132135
- 30. Honma K, Honma S, Hiroshige T (1986) Disorganization of the rat activity rhythm by chronic treatment with methamphetamine. Physiol Behav 38: 687–695.K. HonmaS. HonmaT. Hiroshige1986Disorganization of the rat activity rhythm by chronic treatment with methamphetamine.Physiol Behav38687695
- 31. Mohawk JA, Baer ML, Menaker M (2009) The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes. Proc Natl Acad Sci USA 106: 3519–3524.JA MohawkML BaerM. Menaker2009The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes.Proc Natl Acad Sci USA10635193524
- 32. Stephan FK (1983) Circadian rhythm dissociation induced by periodic feeding in rats with suprachiasmatic lesions. Behav. Brain Res 7: 81–98.FK Stephan1983Circadian rhythm dissociation induced by periodic feeding in rats with suprachiasmatic lesions. Behav.Brain Res78198
- 33. Froy O, Chapnik N, Miskin R (2008) The suprachiasmatic nuclei are involved in determining circadian rhythms during restricted feeding. Neuroscience 155: 1152–1159.O. FroyN. ChapnikR. Miskin2008The suprachiasmatic nuclei are involved in determining circadian rhythms during restricted feeding.Neuroscience15511521159
- 34. Mendoza J, Drevet K, Pevet P, Challet E (2008) Daily meal timing is not necessary for resetting the main circadian clock by calorie restriction. J Neuroendocrinol 20: 251–260.J. MendozaK. DrevetP. PevetE. Challet2008Daily meal timing is not necessary for resetting the main circadian clock by calorie restriction.J Neuroendocrinol20251260
- 35. Daan S, Spoelstra K, Albrecht U, Schmutz I, Daan M, Daan B, Riensk F, Poletaeva I, Dell'Omo G, Vyssotski A, Lipp H-P (2011) Lab mice in the field: unexpected activity patterns and effects of a dysfunctional mPer2 allele. J Biol Rhythms 26: S. DaanK. SpoelstraU. AlbrechtI. SchmutzM. DaanB. DaanF. RienskI. PoletaevaG. Dell'OmoA. VyssotskiH-P Lipp2011Lab mice in the field: unexpected activity patterns and effects of a dysfunctional mPer2 allele.J Biol Rhythms 26in press. in press.