A fundamental property of circadian rhythms is that they resynchronize (i.e., reentrain) to phase shifts of the light-dark cycle-a phenomenon which humans experience as """"""""jet-lag"""""""". Reentrainment to phase shifts of the light-dark cycle has been documented for such a wide variety of species that its occurrence is no longer considered noteworthy. A remarkable and unique exception to this rule has recently been found in Siberian hamsters (Phodopus sungorus sungorus). We found that, unlike other organisms, they fail to reentrain to a 5 hour phase delay or advance of the photocycle; rather, their circadian body temperature and activity rhythms persist (i.e., free run) for several months despite the continued presence of the photocycle. This finding represents the first, time that any mammal has failed to reentrain to commonly used laboratory lighting conditions. This research challenges current theories of entrainment and provides an opportunity to refine those theories. The phase-shifting paradigm that we have developed, allows us to easily and predictably break entrainment. We can, therefore, identify and quantify the factors that facilitate reentrainment to light-dark cycles. The model that we have proposed to explain our data suggests that similar processes underlie entrainment in other species, but are robustly expressed in Siberian hamsters. This may be, in art, because they originate from high latitudes and have adapted to extreme seasonal changes in daylength. Our first goal, therefore, is to evaluate how tau, the photic PRC, and zeitgeber efficacy are altered by phase shifts of the photocycle because these three variables determine entrainment. We will then test predictions made by our two-component model, which we believe explains much of our data, to determine if the effects of light on the pacemaker are dependent on circadian phase and photoperiod. Once these studies are completed, our next goal will be to elucidate how light affects the physiological mechanisms of these pacemaker properties. Specifically, we will evaluate whether melatonin is necessary and/or sufficient for entrainment and then investigate how melatonin alters tau, the photic PRC, and zeitgeber efficacy. We chose to focus on melatonin because its effects on the circadian system of Siberian hamsters suggest a role for this hormone in entrainment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060385-02
Application #
6392646
Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (01))
Program Officer
Heart, Lung, and Blood Inst, National
Project Start
2000-05-10
Project End
2005-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
2
Fiscal Year
2001
Total Cost
$197,311
Indirect Cost
Name
Stanford University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Meredith, Andrea L; Wiler, Steven W; Miller, Brooke H et al. (2006) BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output. Nat Neurosci 9:1041-9
Barakat, Monique T; O'Hara, Bruce F; Cao, Vinh H et al. (2005) Light induces c-fos and per1 expression in the suprachiasmatic nucleus of arrhythmic hamsters. Am J Physiol Regul Integr Comp Physiol 289:R1381-6
Ruby, Norman F; Barakat, Monique T; Heller, H Craig (2004) Phenotypic differences in reentrainment behavior and sensitivity to nighttime light pulses in siberian hamsters. J Biol Rhythms 19:530-41
Barakat, Monique T; O'Hara, Bruce F; Cao, Vinh H et al. (2004) Light pulses do not induce c-fos or per1 in the SCN of hamsters that fail to reentrain to the photocycle. J Biol Rhythms 19:287-97
Larkin, Jennie E; Yokogawa, Tohei; Heller, H Craig et al. (2004) Homeostatic regulation of sleep in arrhythmic Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 287:R104-11
Ruby, Norman F (2003) Hibernation: when good clocks go cold. J Biol Rhythms 18:275-86
Ruby, Norman F; Joshi, Nirav; Heller, H Craig (2002) Constant darkness restores entrainment to phase-delayed Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 283:R1314-20
Ruby, Norman F; Brennan, Thomas J; Xie, Xinmin et al. (2002) Role of melanopsin in circadian responses to light. Science 298:2211-3