Regularly scheduled voluntary exercise synchronizes the mouse circadian clock

1991 ◽  
Vol 261 (4) ◽  
pp. R928-R933 ◽  
Author(s):  
D. M. Edgar ◽  
W. C. Dement

Circadian rhythm entrainment has long been thought to depend exclusively on periodic cues in the external environment. However, evidence now suggests that appropriately timed vigorous activity may also phase shift the circadian clock. Previously it was not known whether levels of exercise/activity associated with spontaneous behavior provided sufficient feedback to phase shift or synchronize circadian rhythms. The present study investigated this issue by monitoring the sleep-wake, drinking, and wheel-running circadian rhythms of mice (Mus musculus) during unrestricted access to running wheels and when free wheel rotation was limited to either 12- or 6-h intervals with a fixed period of 24 h. Wheel rotation was controlled remotely. Mice spontaneously ran in wheels during scheduled access, and free-running sleep-wake and drinking circadian rhythms became entrained to scheduled exercise in 11 of 15 animals. However, steady-state entrainment was achieved only when exercise commenced several hours into the subjective night. The temporal placement of running during entrainment was related (r = 0.7003, P less than 0.02) to free-running period before entrainment. Mice with a free-running period less than 23.0 h did not entrain but exhibited relative coordination between free-running variables and the wheel availability schedule. Thus the circadian timekeeping system responds to temporal feedback arising from the timing of volitional exercise/activity, suggesting that the biological clock not only is responsive to periodic geophysical events in the external environment but also derives physiological feedback from the spontaneous activity behaviors of the organism.

1984 ◽  
Vol 247 (2) ◽  
pp. R250-R256
Author(s):  
H. G. Scholubbers ◽  
W. Taylor ◽  
L. Rensing

Membrane properties of whole cells of Gonyaulax polyedra were measured by fluorescence polarization. Circadian changes of fluorescence polarization exist in exponentially growing cultures. They show an amplitude larger than that of stationary cultures, indicating that a part of the change is due to or amplified by an ongoing cell cycle. Measurements of parameters of the circadian glow rhythm were analyzed for possible correlation with the membrane data. Considerable differences (Q10 = 2.5-3.0) in fluorescence polarization were found in cultures kept at different temperatures ranging from 15 to 27.5 degrees C. The free-running period length at different temperatures, on the other hand, differed only slightly (Q10 = 0.9-1.1). Stationary cultures showed higher fluorescence polarization compared with growing cultures, whereas the free-running period lengths did not differ in cultures of various densities and growth rates. Temperature steps of different sign changed the fluorescence polarization slightly in different directions. The phase shift of 4-h pulses (-5, -9, +7 degrees C) resulted in maximal phase advances of 4, 6, and 2 h, respectively. The phasing of the phase-response curves was identical in all these experiments, a finding not to be expected if the pulses act via the measured membrane properties. Pulses of drugs that change the fluorescence polarization (e.g., chlorpromazine and lidocaine) did not or only slightly phase-shift the circadian rhythm.


1981 ◽  
Vol 241 (1) ◽  
pp. R62-R66 ◽  
Author(s):  
H. E. Albers

The circadian wheel-running rhythms of gonadectomized adult male, female, and perinatally androgenized female rats, maintained in constant darkness, were examined before and after implantation of Silastic capsules containing cholesterol (C) or estradiol-17 beta (E). The free-running period of the activity rhythm (tau) before capsule implantation tended to be shorter in animals exposed to perinatal androgen. Administration of C did not reliably alter tau in any group. E significantly shortened tau in 100% of females injected with oil on day 3 of life. In females, injected with 3.5 micrograms testosterone propionate on day 3, and males, E shortened or lengthened tau, with the direction and magnitude of this change in tau inversely related to the length of the individual's pretreatment tau. These data indicate that the presence of perinatal androgen does not eliminate the sensitivity of the circadian system of the rat to estrogen, since estrogen alters tau in a manner that depends on its pretreatment length.


1999 ◽  
Vol 277 (3) ◽  
pp. R812-R828 ◽  
Author(s):  
B. Pitrosky ◽  
R. Kirsch ◽  
A. Malan ◽  
E. Mocaer ◽  
P. Pevet

Daily administration of melatonin or S20098, a melatonin agonist, is known to entrain the free-running circadian rhythms of rats. The effects of the duration of administration on entrainment were studied. The animals demonstrated free-running circadian rhythms (running-wheel activity, body temperature, general activity) in constant darkness. Daily infusions of melatonin or S20098 for 1, 8, or 16 h entrained the circadian rhythms to 24 h. Two daily infusions of 1 h (separated by 8 h) entrained the activity peak within the shorter time interval. The entraining properties of melatonin and S20098 were similar and were affected neither by pinealectomy nor by infusion of 1- or 8-h duration. However, with 16-h infusion, less than half of the animals became entrained. Once entrained, the phase angle between the onset of infusion and the rhythms (onset of activity or acrophase of body temperature) increased with the duration of infusion. Before entrainment, the free-running period increased with the duration of infusion, an effect that was not predictable from the phase response curve.


2022 ◽  
Author(s):  
Yanli Xiang ◽  
Thomas Sapir ◽  
Pauline Rouillard ◽  
Marina Ferrand ◽  
Jose M Jimenez-Gomez

Many biological processes follow circadian rhythmicity and are controlled by the circadian clock. Predictable environmental changes such as seasonal variation in photoperiod can modulate circadian rhythms, allowing organisms to adjust to the time of the year. Modification of circadian clocks is especially relevant in crops to enhance their cultivability in specific regions by changing their sensibility to photoperiod. In tomato, the appearance of mutations in EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1, Solyc09g075080) and NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 2 (LNK2, Solyc01g068560) during domestication delayed its circadian rhythms, and allowed its expansion outside its equatorial origin. Here we study how variation in circadian rhythms in tomato affects its perception of photoperiod. To do this, we create near isogenic lines carrying combinations of wild alleles of EID1 and LNK2 and perform transcriptomic profiling under two different photoperiods. We observe that EID1, but not LNK2, has a large effect on the tomato transcriptome and its response to photoperiod. This large effect of EID1 is likely a consequence of the global phase shift elicited by this gene in tomato's circadian rhythms.


1982 ◽  
Vol 242 (3) ◽  
pp. R261-R264 ◽  
Author(s):  
P. W. Cheung ◽  
C. E. McCormack

These experiments were undertaken to determine if the pineal gland is involved in the physiological mechanism by which the rat alters its free-running period (tau) in response to changes in illuminance. Spontaneous wheel-running activity was recorded from pinealectomized or sham-operated female Charles River rats. The tau of running activity was determined in continuous darkness (DD) or in continuous dim light (LL). Pinealectomized rats and sham-operated rats lengthened their tau's to approximately the same extent when shifted from DD to LL and shortened their tau's when shifted back to DD. Continuous melatonin administration via Silastic capsules failed to alter tau of rats kept in dim LL. These results indicate that the pineal is not primarily involved in the mechanism by which the rat alters tau in response to changes in illuminance.


1998 ◽  
Vol 275 (4) ◽  
pp. R960-R968 ◽  
Author(s):  
Fred C. Davis ◽  
N. Viswanathan

The causes of age-related disruptions in the timing of human sleep and wakefulness are not known but may include changes in both the homeostatic and circadian regulation of sleep. In Syrian hamsters the free running period of the circadian activity/rest rhythm has been reported to shorten with age. Although this has been observed under a variety of experimental conditions, the changes have been small and their consistency uncertain. In the present study, the wheel running activity/rest rhythm was continuously measured in male Syrian hamsters ( Mesocricetus auratus) in dim constant light (<1 lx) from 8 wk of age until death. Fifteen hamsters survived to at least 90 wk (28%). The average free running period of these hamsters did not change with age. In 18 hamsters that died between 50 and 88 wk, free running period also did not change before death. In contrast to free running period, other measures related to activity level changed significantly with age and before death. Despite changes in the expression of the activity/rest rhythm, the free running period of the hamster circadian pacemaker remained remarkably stable with age.


2021 ◽  
Author(s):  
Yoshiaki Yamaguchi ◽  
Iori Murai ◽  
Kaoru Goto ◽  
Shotaro Doi ◽  
Huihua Zhou ◽  
...  

Background and Purpose: Gpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with no established physiological function in vivo. The purpose of this study was to determine the role of Gpr19 in the circadian clock system. Experimental Approach: We examined whether and how the master circadian clock neurons in the suprachiasmatic nucleus (SCN) express Gpr19. By analysing Gpr19-deficient (Gpr19−/−) mice, we asked whether Gpr19 has a role in modulating free-running period and light resetting capacity of the circadian clock. Key Results: Compared with the known common core clock genes, Gpr19 was identified to show several distinct yet limited features related to the circadian clock. Gpr19 mRNA was mainly expressed in the middle-to-dorsal region of the SCN. A conserved cAMP-responsive element within the Gpr19 promoter drove the circadian expression of Gpr19. Gpr19−/− mice exhibited a prolonged circadian period and a delayed initiation of daily locomotor activity in a 12-h light/12-h dark cycle. Gpr19 deficiency caused the downregulation of several genes that normally peak during the night, including Bmal1 and Gpr176. Gpr19−/− mice had a reduced capacity for phase shift to early subjective night light. The defect was only observed for phase-delay, but not phase-advance, and accompanied by reduced response of c-Fos expression in the dorsal region of the SCN, while apparently normal in the ventral part of the SCN, in Gpr19−/− mice. Conclusion and Implications: Gpr19 is an SCN-enriched orphan GPCR with a distinct role in circadian regulation and thus may be a potential target for alleviating circadian clock disorders.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshiaki Yamaguchi ◽  
Iori Murai ◽  
Kaoru Goto ◽  
Shotaro Doi ◽  
Huihua Zhou ◽  
...  

AbstractGpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with currently no established physiological role in vivo. We characterized Gpr19 expression in the suprachiasmatic nucleus (SCN), the locus of the master circadian clock in the brain, and determined its role in the context of the circadian rhythm regulation. We found that Gpr19 is mainly expressed in the dorsal part of the SCN, with its expression fluctuating in a circadian fashion. A conserved cAMP-responsive element in the Gpr19 promoter was able to produce circadian transcription in the SCN. Gpr19−/− mice exhibited a prolonged circadian period and a delayed initiation of daily locomotor activity. Gpr19 deficiency caused the downregulation of several genes that normally peak during the night, including Bmal1 and Gpr176. In response to light exposure at night, Gpr19−/− mice had a reduced capacity for light-induced phase-delays, but not for phase-advances. This defect was accompanied by reduced response of c-Fos expression in the dorsal region of the SCN, while apparently normal in the ventral area of the SCN, in Gpr19−/− mice. Thus, our data demonstrate that Gpr19 is an SCN-enriched orphan GPCR with a distinct role in circadian regulation and may provide a potential target option for modulating the circadian clock.


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