Circadian Rhythm of Output from Neurones in the Eye of Aplysia: III. Effects of Light on Clock and Receptor Output Measured in the Optic Nerve

1977 ◽  
Vol 70 (1) ◽  
pp. 183-194
Author(s):  
JACK A. BENSON ◽  
JON W. JACKLET
Keyword(s):  
Circadian Rhythm ◽  
Optic Nerve ◽  
Circadian Clock ◽  
Light Pulse ◽  
Temperature Sensitivity ◽  
Phase Point ◽  
Light Onset ◽  
Constant Illumination ◽  
Light Pulses ◽  
East West

1. The circadian rhythm of CAP frequency recorded from the optic nerve of isolated eyes at 15 °C was damped out by constant illumination (1100 lux) after several cycles of the rhythm. During illumination (LL) the rhythm was skewed with a rapid rising phase and slow falling phase, and the period was decreased by about 1 h. It is postulated that the circadian clock was stopped by LL at its lowest phase point, and that following cessation of LL, the rhythm was reinitiated from this phase point after a latency of 6-8 h. 2. For light pulses of 80 lux and 1100 lux, the photoresponse of the dark-adapted eye to 20 min light pulses applied beginning at 2 h intervals was not influenced by the circadian clock. At 5 lux there was a periodicity in the magnitude of the photoresponse, in phase with the circadian rhythm of spontaneous CAP production. 3. Small CAPs of non-circadian frequency were recorded together with normal CAPs in about 10% of records of output from isolated eyes. The cells producing the small CAPs had a different temperature sensitivity from those producing normal CAPs. The response of these cells to short light pulses consisted of a phasic burst of activity at light onset, followed by silence during the remainder of the short light pulse, and for 1 or 2 min following cessation of illumination. These small CAPs may be the activity either of H-type receptors or of secondary cells desynchronized from the major population. Note: Laboratory of Sensory Sciences, University of Hawaii at Manoa, 1993 East-West Road, Honolulu, Hawaii 96822, U.S.A.

Circadian Rhythm of Output from Neurones in the Eye of Aplysia: II. Effects of Cold Pulses on a Population of Coupled Oscillators

1977 ◽  
Vol 70 (1) ◽  
pp. 167-181
Author(s):  
JACK A. BENSON ◽  
JON W. JACKLET
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Coupled Oscillators ◽  
Phase Point ◽  
Frequency Curve ◽  
Phase Angle Difference ◽  
Long Duration ◽  
Large Phase ◽  
East West ◽  
Frequency Curves

1. The circadian clock that controls CAP frequency was stopped at or near its lowest phase point by long duration cold pulses of 6 °C. On return to normal recording temperature (15 °C), the rhythm was always reinitiated from this phase point. 2. Following long cold pulses, there was often a transient peak of CAP activity lasting 2-6 h. It is thought that this was an effect of rise in temperature after prolonged cooling and not an effect on the clock itself. 3. Twelve h cold pulses, spanning the rhythm peak, caused phase delays. 9 °C pulses caused small delays (e.g. 1.7 h) while large phase delays (e.g. 6.7 h) followed pulses of 5 °C. Some pulses at an intermediate temperature (8.5 °C) caused abnormal post-pulse cycles lasting several days, and resulting in very large phase delays (10–14 n). 4. The abnormal CAP frequency curves following 12 h cold pulses of 8.5 °C spanning the rhythm peak are interpreted as rhythm splits. It is postulated that part of the population of coupled oscillators comprising the circadian clock was slightly delayed by the cold pulse, while the other part was driven further towards the “stopped” state, thus producing a large phase angle difference between the two subpopulations. These drew one another back into phase during several cycles to reform a normal circadian rhythm. 5. It is hypothesized that the circadian oscillations of the two subpopulations did not sum to produce the observed CAP frequency curve; rather the level of CAP output was controlled by whichever subpopulation was discharging at the higher frequency. Note: Laboratory of Sensory Sciences, University of Hawaii at Manoa, 1993 East-West Road, Honolulu, Hawaii 96822, U.S.A.

Differential effects of bright light and social cues on reentrainment of human circadian rhythms

1995 ◽  
Vol 268 (2) ◽  
pp. R528-R535 ◽  
Author(s):  
K. Honma ◽  
S. Honma ◽  
K. Nakamura ◽  
M. Sasaki ◽  
T. Endo ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Phase Shift ◽  
Light Pulse ◽  
Bright Light ◽  
Maximum Phase ◽  
Differential Effects ◽  
Light Pulses ◽  
Human Circadian Rhythm ◽  
The Social ◽  
Temperature Rhythms

Reentrainment of human circadian rhythm to an 8-h advanced schedule of sleep and social contacts was assessed under two different conditions: with and without bright light (4,000-6,000 lx). Subjects spent 15 days without knowing the natural day-night alternation. On the fourth day, the social schedule was phase-advanced by 8 h. In one experiment, a bright light pulse of 3-h duration was given in every subjective morning, and in the other no light pulse was applied. Plasma melatonin and rectal temperature rhythms were measured. Seven of nine subjects showed an orthodromic phase shift, the rate of which was significantly larger with bright light pulses than without them. The maximum phase-advance shift by three consecutive light pulses was observed when the first pulse was applied approximately 4 h after the onset of melatonin rise. By contrast, the maximum phase shift of a similar extent was detected at 1 h after the onset of melatonin rise, when ordinary room light (300-500 lx) at the time corresponding to bright light was regarded as a dim light pulse. It is concluded that bright light accelerates the reentrainment of human circadian rhythm, and bright light and social schedule have differential effects on the reentrainment.

scholarly journals Altered Light Sensitivity of Circadian Clock in Shank3+/– Mouse

2021 ◽  
Vol 15 ◽  
Author(s):  
Javier Alamilla ◽  
Yazmín Ramiro-Cortés ◽  
Adriana Mejía-López ◽  
José-Luis Chavez ◽  
Dulce Olivia Rivera ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Neurodevelopmental Disorder ◽  
Red Light ◽  
Bright Light ◽  
Light Sensitivity ◽  
Autism Spectrum ◽  
Constant Darkness ◽  
Light Pulses ◽  
Immunohistochemical Techniques

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan–McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3+/– mouse, to study the circadian rhythm architecture of locomotion behavior and its entrainment to light. We also analyzed the synapse between the retinohypothalamic tract (RHT) and the suprachiasmatic nucleus (SCN), employing tract tracing and immunohistochemical techniques. We found that Shank3+/– mice were not impaired in the SCN circadian clock, as indicated by a lack of differences between groups in the circadian architecture in entrained animals to either long or short photoperiods. Circadian rhythm periodicity (tau) was unaltered between genotypes in constant darkness (DD, dim red light). Similar results were obtained in the re-entrainment to shifts in the light–dark cycle and in the entrainment to a skeleton photoperiod from DD. However, Shank3+/– mice showed larger phase responses to light pulses, both delays and advances, and rhythm disorganization induced by constant bright light. Immunohistochemical analyses indicated no differences in the RHT projection to the SCN or the number of SCN neurons expressing the N-methyl-D-aspartate (NMDA) receptor subunit NR2A, whereas the Shank3+/– animals showed decreased c-Fos induction by brief light pulses at CT14, but increased number of vasoactive intestinal polypeptide (VIP)-positive neurons. These results indicate alterations in light sensitivity in Shank3+/– mice. Further studies are necessary to understand the mechanisms involved in such increased light sensitivity, probably involving VIP neurons.

scholarly journals PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 266
Author(s):  
Juan Alfonso Redondo ◽  
Romain Bibes ◽  
Alizée Vercauteren Drubbel ◽  
Benjamin Dassy ◽  
Xavier Bisteau ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Circadian Rhythm ◽  
Survival Rate ◽  
Circadian Clock ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Response To Therapy ◽  
Circadian Oscillation ◽  
Resistance To Therapy

Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor relapse. To effectively reduce the mortality rate of this disease, we need to better understand the molecular mechanisms underlying the development of resistance to therapy and translate that knowledge into novel approaches for cancer treatment. The circadian clock orchestrates several physiological processes through the establishment and synchronization of circadian rhythms. Since cancer cells need to fuel rapid proliferation and increased metabolic demands, the escape from circadian rhythm is relevant in tumorigenesis. Although clock related genes may be globally repressed in human eSCC samples, PER2 expression still oscillates in some human eSCC cell lines. However, the consequences of this circadian rhythm are still unclear. In the present study, we confirm that PER2 oscillations still occur in human cancer cells in vitro in spite of a deregulated circadian clock gene expression. Profiling of eSCC cells by RNAseq reveals that when PER2 expression is low, several transcripts related to apoptosis are upregulated. Consistently, treating eSCC cells with cisplatin when PER2 expression is low enhances DNA damage and leads to a higher apoptosis rate. Interestingly, this process is conserved in a mouse model of chemically-induced eSCC ex vivo. These results therefore suggest that response to therapy might be enhanced in esophageal cancers using chronotherapy.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

Effect of somatostatin on circadian rhythms of firing and 2-deoxyglucose uptake in rat suprachiasmatic slices

1993 ◽  
Vol 265 (5) ◽  
pp. R1199-R1204 ◽  
Author(s):  
T. Hamada ◽  
S. Shibata ◽  
A. Tsuneyoshi ◽  
K. Tominaga ◽  
S. Watanabe
Keyword(s):  
Circadian Rhythm ◽  
Vasoactive Intestinal Polypeptide ◽  
Phase Changes ◽  
Circadian Clocks ◽  
Constant Darkness ◽  
Phase Resetting ◽  
Firing Activity ◽  
Light Pulses ◽  
Circadian Time

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus appears to act as a circadian clock. The SCN vasoactive intestinal polypeptide-like immunoreactive neurons, which may act to mediate photic information in the SCN, receive input from neurons immunoreactive for somatostatin (SST). Therefore we investigated the role of SST as a transmitter for entrainment by analyzing the phase-resetting effect of SST on the circadian rhythm of SCN firing activity. Perfusion of SST increased 2-deoxyglucose uptake at circadian time (CT) 18, but not at CT6. A 1-h or 15-min treatment with SST produced phase delays when it was administered at CT13-14 and phase advances at CT22-23. Thus SST-induced phase changes are similar to those for light pulses to animals under constant darkness. The present findings suggest that SST is a transmitter for mediating information of entrainment to circadian clocks within the SCN.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: A sense of time of the glucocorticoid circadian clock: from the ontogeny to the diagnosis of Cushing’s syndrome

2018 ◽  
Vol 179 (1) ◽  
pp. R1-R18 ◽  
Author(s):  
Ayrton Custodio Moreira ◽  
Sonir Rauber Antonini ◽  
Margaret de Castro
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Clock Genes ◽  
Circadian Variation ◽  
Circadian System ◽  
Feedback Loops ◽  
Adrenal Axis ◽  
Sense Of Time ◽  
Pituitary Adrenal Axis ◽  
Hierarchical Manner

The circadian rhythm of glucocorticoids has long been recognised within the last 75 years. Since the beginning, researchers have sought to identify basic mechanisms underlying the origin and emergence of the corticosteroid circadian rhythmicity among mammals. Accordingly, Young, Hall and Rosbash, laureates of the 2017 Nobel Prize in Physiology or Medicine, as well as Takahashi’s group among others, have characterised the molecular cogwheels of the circadian system, describing interlocking transcription/translation feedback loops essential for normal circadian rhythms. Plasma glucocorticoid circadian variation depends on the expression of intrinsic clock genes within the anatomic components of the hypothalamic–pituitary–adrenal axis, which are organised in a hierarchical manner. This review presents a general overview of the glucocorticoid circadian clock mechanisms, highlighting the ontogeny of the pituitary–adrenal axis diurnal rhythmicity as well as the involvement of circadian rhythm abnormalities in the physiopathology and diagnosis of Cushing’s disease.

Abstract 3: Cellular Contributions of the Circadian Clock in Atherogenesis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Xueling Li ◽  
Ling Ruan ◽  
Austin Bentley ◽  
Stephen Haigh ◽  
Yuqing Huo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Circadian Rhythm ◽  
Circadian Clock ◽  
Cell Types ◽  
No Production ◽  
Light Cycle ◽  
Lipid Uptake ◽  
Enhanced Production ◽  
The Impact

Atherosclerosis is a leading cause of death despite the improvements in lipid and blood pressure control. The circadian clock, a molecular network of genes and proteins that controls 24-hour timing, has emerged to have a surprising role in the control of metabolic and vascular function. Herein we examined the impact of circadian rhythm dysfunction in atherogenesis by implementation of vascular transplant and PCSK9 based approaches to induce accelerated lesion development in mice. We find that atherogenesis is exacerbated in Bmal1-KO aortic grafts immersed in the hypercholesterolemic milieu of ApoE -/- mice. To assess if atherosclerosis was ‘circadian rhythm dependent’ we subjected wild-type mice to a shortened light cycle (4L/4D) and induced atherosclerosis by intravenous injection of a human PCSK-9 adeno associated virus. Atherosclerosis in the jet-lagged PCSK-9 mice was robustly increased relative to the atherosclerosis observed in WT mice on a normal light cycle (12L/12D), providing further evidence that circadian rhythm and the circadian clock contribute to atherosclerosis. However, atherosclerosis is a complex disease that is the net result of interplay between intrinsic (vascular cells) and extrinsic mechanisms (metabolism, blood pressure, and hormones) and the importance of clock function in individual cell types is poorly understood. We found that deletion or silencing of key circadian transcription factors resulted in an enhanced inflammatory and pro-oxidant phenotype with diminished NO production and greater lipid uptake in both macrophages and endothelial cells. Loss of circadian function in smooth muscle cells similarly resulted in enhanced production of reactive oxygen species and greater cell proliferation. Surprising, the silencing of Bmal2 in endothelial cells resulted in greater lipid uptake in oxLDL treated HAEC as well as increased expression of markers of autophagy, suggesting that Bmal2 may orchestrate numerous output functions in different cell types. In conclusion, we find that the circadian clock and circadian rhythm have a profound impact on atherosclerosis, to influence vascular cell inflammatory and lipid uptake responses, and identify an unexpectedly prominent role for the side-partner of Bmal1, Bmal2.

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