Emergence of altered circadian timing in a cholinergically supersensitive rat line

1999 ◽  
Vol 277 (4) ◽  
pp. R1171-R1178 ◽  
Author(s):  
Sally A. Ferguson ◽  
David J. Kennaway
Keyword(s):  
Onset Time ◽  
Neural Pathways ◽  
Suprachiasmatic Nuclei ◽  
Circadian Timing ◽  
Temperature Rhythm ◽  
Circadian Timing System ◽  
Free Running ◽  
Light Effects ◽  
Free Running Period

Mammalian circadian rhythms are controlled by the suprachiasmatic nuclei (SCN) in concert with light information. Several neurotransmitters and neural pathways modulate light effects on SCN timing. This study used a line of rat with an upregulated cholinergic system to investigate the role of acetylcholine in rhythmicity. With the use of a selective breeding program based on the thermic response to a cholinergic agonist, we developed a supersensitive (Sox) and subsensitive (Rox) rat line. The Sox rats showed an earlier onset time of melatonin rhythm under a 12:12-h light-dark photoperiod from generation 3 (3 ± 0.5 h after dark) compared with Rox rats (4.5 ± 0.1 h) and an earlier morning decline in temperature (0.9 ± 0.3 h before lights on) compared with Rox animals (0.1 ± 0.1 h). Furthermore, the Soxanimals displayed a significantly shorter free-running period of temperature rhythm than Rox rats (23.9 ± 0.04 and 24.3 ± 0.1 h, respectively, P < 0.05). The results suggest that the altered circadian timing of the Sox rats may be related to the cholinergic supersensitivity, intimating a role for acetylcholine in the circadian timing system.

Role of the suprachiasmatic nuclei in the circadian timing system of the squirrel monkey. I. The generation of rhythmicity

1984 ◽  
Vol 300 (2) ◽  
pp. 275-284 ◽  
Author(s):  
H. Elliott Albers ◽  
Ralph Lydic ◽  
Philippa H. Gander ◽  
Martin C. Moore-Ede
Keyword(s):  
Squirrel Monkey ◽  
Suprachiasmatic Nuclei ◽  
Circadian Timing ◽  
Timing System ◽  
Circadian Timing System

scholarly journals Metabolic disturbances: role of the circadian timing system and sleep

2016 ◽  
Vol 8 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Navin Adhikary ◽  
Santosh Lal Shrestha ◽  
Jia Zhong Sun
Keyword(s):  
Metabolic Disturbances ◽  
Circadian Timing ◽  
Timing System ◽  
Circadian Timing System

Light effects on circadian timing system of a diurnal primate, the squirrel monkey

1985 ◽  
Vol 249 (2) ◽  
pp. R274-R280 ◽  
Author(s):  
T. M. Hoban ◽  
F. M. Sulzman
Keyword(s):  
Squirrel Monkey ◽  
Response Curve ◽  
Phase Response Curve ◽  
Phase Response ◽  
Day Length ◽  
Circadian Timing ◽  
Subjective Night ◽  
Timing System ◽  
Circadian Timing System ◽  
Light Effects

We examined light effects on the circadian timing system of the squirrel monkey. A phase-response curve to 1-h pulses of light was constructed for the drinking rhythm of six animals. The phase-response curve was the same type as that exhibited by nocturnal rodents, with phase delays occurring early in the subjective night and phase advances late in the subjective night. The range of entrainment of 10 monkeys to days with 1 h light and x h dark was determined. Five monkeys used to generate the phase-response curve were also used in the range of entrainment determination. For short light-dark cycles the range of entrainment was smaller than that expected, with no monkey entraining to a day length of less than 23.5 h.

scholarly journals Reduced VIP Expression Affects Circadian Clock Function in VIP-IRES-CRE Mice (JAX 010908)

2020 ◽  
Vol 35 (4) ◽  
pp. 340-352 ◽  
Author(s):  
Deborah A. M. Joye ◽  
Kayla E. Rohr ◽  
Danielle Keller ◽  
Thomas Inda ◽  
Adam Telega ◽  
...  
Keyword(s):  
Constant Darkness ◽  
Wild Type ◽  
Free Running ◽  
Dna Editing ◽  
Editing Enzyme ◽  
Free Running Period ◽  
Precise Role ◽  
Insight Into ◽  
Master Clock

Circadian rhythms are programmed by the suprachiasmatic nucleus (SCN), which relies on neuropeptide signaling to maintain daily timekeeping. Vasoactive intestinal polypeptide (VIP) is critical for SCN function, but the precise role of VIP neurons in SCN circuits is not fully established. To interrogate their contribution to SCN circuits, VIP neurons can be manipulated specifically using the DNA-editing enzyme Cre recombinase. Although the Cre transgene is assumed to be inert by itself, we find that VIP expression is reduced in both heterozygous and homozygous adult VIP-IRES-Cre mice (JAX 010908). Compared with wild-type mice, homozygous VIP-Cre mice display faster reentrainment and shorter free-running period but do not become arrhythmic in constant darkness. Consistent with this phenotype, homozygous VIP-Cre mice display intact SCN PER2::LUC rhythms, albeit with altered period and network organization. We present evidence that the ability to sustain molecular rhythms in the VIP-Cre SCN is not due to residual VIP signaling; rather, arginine vasopressin signaling helps to sustain SCN function at both intracellular and intercellular levels in this model. This work establishes that the VIP-IRES-Cre transgene interferes with VIP expression but that loss of VIP can be mitigated by other neuropeptide signals to help sustain SCN function. Our findings have implications for studies employing this transgenic model and provide novel insight into neuropeptide signals that sustain daily timekeeping in the master clock.

The Suprachiasmatic Nucleus

2017 ◽  
pp. 111-118
Author(s):  
Gabriella Lundkvist ◽  
Gene D. Block
Keyword(s):  
Circadian Rhythm ◽  
Optic Chiasm ◽  
Diurnal Variations ◽  
Biological Clocks ◽  
Cellular Interactions ◽  
Suprachiasmatic Nuclei ◽  
Circadian Timing ◽  
Timing System ◽  
Circadian Timing System ◽  
And Behavior

Diurnal variations in physiology and behavior are ubiquitous in higher organisms. Although some rhythms are driven directly by geophysical cycles of light or temperature, most are generated by internal timers, commonly referred to as biological clocks. In mammals, including humans, these circadian (near 24-h) properties are controlled by a central timer formed by a distinct regional network in the anterior hypothalamus close to the optic chiasm, the bilateral suprachiasmatic nuclei (SCN). Rodents, with their SCN lesioned, fail to exhibit diurnal variations in behavior. The mechanism generating rhythmicity is contained within individual neurons; however, many of the properties of the circadian timing system derive from cellular interactions within SCN. These microcircuits give rise to a functional clock capable of maintaining a circadian rhythm with a stable period and phase and driving or synchronizing circadian rhythms in other tissues.

scholarly journals Circadian rhythms and reproduction

Reproduction ◽  
2006 ◽  
Vol 132 (3) ◽  
pp. 379-392 ◽  
Author(s):  
Michael J Boden ◽  
David J Kennaway
Keyword(s):  
Circadian Rhythms ◽  
Reproductive Performance ◽  
Clock Genes ◽  
Strain Differences ◽  
Reproductive Function ◽  
Circadian Timing ◽  
Wide Range ◽  
Timing System ◽  
Circadian Timing System

There is a growing recognition that the circadian timing system, in particular recently discovered clock genes, plays a major role in a wide range of physiological systems. Microarray studies, for example, have shown that the expression of hundreds of genes changes many fold in the suprachiasmatic nucleus, liver heart and kidney. In this review, we discuss the role of circadian rhythmicity in the control of reproductive function in animals and humans. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance, but there are sufficient redundancies in their function that many of the knockout mice produced do not show overt reproductive failure. Furthermore, important strain differences have emerged from the studies especially between the variousClock(CircadianLocomotorOutputCycleKaput) mutant strains. Nevertheless, there is emerging evidence that the primary clock genes,ClockandBmal1(Brain andMuscleARNT-like protein 1, also known asMop3), strongly influence reproductive competency. The extent to which the circadian timing system affects human reproductive performance is not known, in part, because many of the appropriate studies have not been done. With the role ofClockandBmal1in fertility becoming clearer, it may be time to pursue the effect of polymorphisms in these genes in relation to the various types of infertility in humans.

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

eLife ◽  
2019 ◽  
Vol 8 ◽  
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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