Pigment-Dispersing Factor Affects Nocturnal Activity Rhythms, Photic Entrainment, and the Free-Running Period of the Circadian Clock in the CricketGryllus bimaculatus

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.

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Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock

10.1101/2021.08.07.455504 ◽

2021 ◽

Author(s):

Yoshiaki Yamaguchi ◽

Iori Murai ◽

Kaoru Goto ◽

Shotaro Doi ◽

Huihua Zhou ◽

...

Keyword(s):

Circadian Clock ◽

Clock Genes ◽

Dorsal Region ◽

Circadian Expression ◽

Delayed Initiation ◽

Free Running ◽

Responsive Element ◽

Free Running Period ◽

Orphan Gpcr

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.

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Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock

Scientific Reports ◽

10.1038/s41598-021-01764-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoshiaki Yamaguchi ◽

Iori Murai ◽

Kaoru Goto ◽

Shotaro Doi ◽

Huihua Zhou ◽

...

Keyword(s):

Circadian Clock ◽

Light Exposure ◽

Physiological Role ◽

Delayed Initiation ◽

Free Running ◽

Responsive Element ◽

Free Running Period ◽

Ventral Area ◽

Orphan Gpcr

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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per mRNA cycling is locked to lights-off under photoperiodic conditions that support circadian feedback loop function.

Molecular and Cellular Biology ◽

10.1128/mcb.16.8.4182 ◽

1996 ◽

Vol 16 (8) ◽

pp. 4182-4188 ◽

Cited By ~ 60

Author(s):

J Qiu ◽

P E Hardin

Keyword(s):

Locomotor Activity ◽

Negative Feedback ◽

Reference Point ◽

Feedback Loop ◽

Negative Feedback Loop ◽

Loop Function ◽

Activity Rhythms ◽

Free Running ◽

Circadian Behavior ◽

Free Running Period

Circadian fluctuations in per mRNA and protein are central to the operation of a negative feedback loop that is necessary for setting the free-running period and for entraining the circadian oscillator to light-dark cycles. In this study, per mRNA cycling and locomotor activity rhythms were measured under different light and dark cycling regimes to determine how photoperiods affect the molecular feedback loop and circadian behavior, respectively. These experiments reveal that per mRNA peaks in abundance 4 h after lights-off in photoperiods of < or = 16 h, that, phase shifts in per mRNA cycling and behavioral rhythmicity occur rapidly after flies are transferred from one photoperiod to another, and that photoperiods longer than 20 h abolish locomotor activity rhythms and leave per mRNA at a median constitutive level. These results indicate that the per feedback loop uses lights-off as a phase reference point and suggest (along with previous findings for per01 and tim01) that per mRNA cycling is not regulated via simple negative feedback from the per protein.

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Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock

eLife ◽

10.7554/elife.50925 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 1

Author(s):

Andrea Brenna ◽

Iwona Olejniczak ◽

Rohit Chavan ◽

Jürgen A Ripperger ◽

Sonja Langmesser ◽

...

Keyword(s):

Circadian Clock ◽

Cyclin Dependent Kinase ◽

Suprachiasmatic Nuclei ◽

Nuclear Entry ◽

Period 2 ◽

Clock Component ◽

Free Running ◽

Free Running Period ◽

Cryptochrome 1 ◽

Cyclin Dependent Kinase 5

Circadian oscillations emerge from transcriptional and post-translational feedback loops. An important step in generating rhythmicity is the translocation of clock components into the nucleus, which is regulated in many cases by kinases. In mammals, the kinase promoting the nuclear import of the key clock component Period 2 (PER2) is unknown. Here, we show that the cyclin-dependent kinase 5 (CDK5) regulates the mammalian circadian clock involving phosphorylation of PER2. Knock-down of Cdk5 in the suprachiasmatic nuclei (SCN), the main coordinator site of the mammalian circadian system, shortened the free-running period in mice. CDK5 phosphorylated PER2 at serine residue 394 (S394) in a diurnal fashion. This phosphorylation facilitated interaction with Cryptochrome 1 (CRY1) and nuclear entry of the PER2-CRY1 complex. Taken together, we found that CDK5 drives nuclear entry of PER2, which is critical for establishing an adequate circadian period of the molecular circadian cycle. Of note is that CDK5 may not exclusively phosphorylate PER2, but in addition may regulate other proteins that are involved in the clock mechanism. Taken together, it appears that CDK5 is critically involved in the regulation of the circadian clock and may represent a link to various diseases affected by a derailed circadian clock.

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Cyclin Dependent Kinase 5 (CDK5) Regulates the Circadian Clock

10.1101/728733 ◽

2019 ◽

Author(s):

Andrea Brenna ◽

Iwona Olejniczak ◽

Rohit Chavan ◽

Jürgen A. Ripperger ◽

Sonja Langmesser ◽

...

Keyword(s):

Circadian Clock ◽

Cyclin Dependent Kinase ◽

Suprachiasmatic Nuclei ◽

Nuclear Entry ◽

Period 2 ◽

Clock Component ◽

Free Running ◽

Free Running Period ◽

Cryptochrome 1 ◽

Cyclin Dependent Kinase 5

AbstractCircadian oscillations emerge from transcriptional and post-translational feedback loops. An important step in generating rhythmicity is the translocation of clock components into the nucleus, which is regulated in many cases by kinases. In mammals, the kinase promoting the nuclear import of the key clock component Period 2 (PER2) is unknown. Here we show that the cyclin-dependent kinase 5 (CDK5) regulates the mammalian circadian clock involving phosphorylation of PER2. Knock-down of Cdk5 in the suprachiasmatic nuclei (SCN), the main coordinator site of the mammalian circadian system, shortened the free-running period in mice. CDK5 phosphorylated PER2 at serine residue 394 (S394) in a diurnal fashion. This phosphorylation facilitated interaction with Cryptochrome 1 (CRY1) and nuclear entry of the PER2-CRY1 complex. Taken together, we found that CDK5 drives nuclear entry of PER2, which is critical for establishing an adequate circadian period of the molecular circadian cycle. Therefore, CDK5 is critically involved in the regulation of the circadian clock and may represent a link to various diseases affected by the circadian clock.

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Nurr1 deficiency shortens free running period, enhances photoentrainment to phase advance, and disrupts circadian cycling of the dopamine neuron phenotype

Behavioural Brain Research ◽

10.1016/j.bbr.2021.113347 ◽

2021 ◽

pp. 113347

Author(s):

Heath S. Partington ◽

Jennifer Makenzie Nutter ◽

Jeffrey B. Eells

Keyword(s):

Dopamine Neuron ◽

Phase Advance ◽

Free Running ◽

Free Running Period

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A circadian clock in a nonphotosynthetic prokaryote

Science Advances ◽

10.1126/sciadv.abe2086 ◽

2021 ◽

Vol 7 (2) ◽

pp. eabe2086

Author(s):

Zheng Eelderink-Chen ◽

Jasper Bosman ◽

Francesca Sartor ◽

Antony N. Dodd ◽

Ákos T. Kovács ◽

...

Keyword(s):

Temperature Compensation ◽

Temporal Structure ◽

Bacterial Biofilm ◽

Circadian Clocks ◽

Industrial Processes ◽

Free Living ◽

Considerable Potential ◽

Free Running ◽

Free Running Period ◽

Constant Dark

Circadian clocks create a 24-hour temporal structure, which allows organisms to occupy a niche formed by time rather than space. They are pervasive throughout nature, yet they remain unexpectedly unexplored and uncharacterized in nonphotosynthetic bacteria. Here, we identify in Bacillus subtilis circadian rhythms sharing the canonical properties of circadian clocks: free-running period, entrainment, and temperature compensation. We show that gene expression in B. subtilis can be synchronized in 24-hour light or temperature cycles and exhibit phase-specific characteristics of entrainment. Upon release to constant dark and temperature conditions, bacterial biofilm populations have temperature-compensated free-running oscillations with a period close to 24 hours. Our work opens the field of circadian clocks in the free-living, nonphotosynthetic prokaryotes, bringing considerable potential for impact upon biomedicine, ecology, and industrial processes.

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Are membrane properties essential for the circadian rhythm of Gonyaulax?

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1984.247.2.r250 ◽

1984 ◽

Vol 247 (2) ◽

pp. R250-R256

Author(s):

H. G. Scholubbers ◽

W. Taylor ◽

L. Rensing

Keyword(s):

Circadian Rhythm ◽

Phase Shift ◽

Fluorescence Polarization ◽

The Other ◽

Membrane Properties ◽

Response Curves ◽

Whole Cells ◽

Different Temperatures ◽

Free Running ◽

Free Running Period

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.

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Gonadal hormones organize and modulate the circadian system of the rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1981.241.1.r62 ◽

1981 ◽

Vol 241 (1) ◽

pp. R62-R66 ◽

Cited By ~ 11

Author(s):

H. E. Albers

Keyword(s):

Testosterone Propionate ◽

Wheel Running ◽

Activity Rhythm ◽

Gonadal Hormones ◽

Circadian System ◽

Female Rats ◽

Constant Darkness ◽

Before And After ◽

Free Running ◽

Free Running Period

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.

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