scholarly journals A Circuit Mechanism Underlying Suppression of Circadian Signals by Homeostatic Sleep Drive

2020 ◽  
Author(s):  
Anna N. King ◽  
Jessica E. Schwarz ◽  
Cynthia T. Hsu ◽  
Annika F. Barber ◽  
Amita Sehgal
Keyword(s):  
Rest Period ◽  
Circadian System ◽  
Daily Cycle ◽  
Sleep Timing ◽  
Recovery Sleep ◽  
Circadian Control ◽  
Sleep Drive ◽  
Output Neurons ◽  
Central Clock ◽  
Homeostatic Mechanisms

AbstractSleep is controlled by homeostatic mechanisms, which drive sleep following periods of wakefulness, and a circadian clock, which regulates sleep timing in a daily cycle. Homeostatic sleep drive sometimes overrides the clock, such that recovery sleep after deprivation occurs outside the normal circadian rest period. However, mechanisms underlying this effect are unknown. We find that sleep-promoting dorsal fan-shaped body (dFB) neurons, effectors of homeostatic sleep in Drosophila, are presynaptic to hugin+ neurons, previously identified as circadian output neurons regulating locomotor activity rhythms. Sleep deprivation decreases hugin+ neuronal activity, which likely suppresses circadian control to promote recovery sleep driven by dFB neurons. Indeed, removal of hugin+ neurons increases sleep-promoting effects of dFB neurons. Trans-synaptic mapping reveals that hugin+ neurons feed back onto s-LNv central clock neurons, which also show Hugin-dependent decreased activity upon sleep loss. These findings identify a circuit-based mechanism through which sleep drive modulates the circadian system to promote recovery sleep following deprivation.

Hugin+ neurons provide a link between sleep homeostat and circadian clock neurons

2021 ◽  
Vol 118 (47) ◽  
pp. e2111183118
Author(s):  
Jessica E. Schwarz ◽  
Anna N. King ◽  
Cynthia T. Hsu ◽  
Annika F. Barber ◽  
Amita Sehgal
Keyword(s):  
Locomotor Activity ◽  
Sleep Deprivation ◽  
Circadian Clock ◽  
Sleep Loss ◽  
Daily Cycle ◽  
Shaped Body ◽  
Recovery Sleep ◽  
Sleep Homeostat ◽  
Central Clock ◽  
Homeostatic Mechanisms

Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that hugin+ neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of hugin+ neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of hugin+ neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the hugin+ locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that hugin+ neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide–dependent fashion. We propose that hugin+ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.

scholarly journals Genomics of circadian rhythms in health and disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Filipa Rijo-Ferreira ◽  
Joseph S. Takahashi
Keyword(s):  
Genetic Regulation ◽  
Treatment Strategies ◽  
Circadian System ◽  
Chromosome Organization ◽  
Metabolic Function ◽  
Genome Wide ◽  
Circadian Control ◽  
Health And Disease ◽  
Genomic Regulation ◽  
The Impact

AbstractCircadian clocks are endogenous oscillators that control 24-h physiological and behavioral processes. The central circadian clock exerts control over myriad aspects of mammalian physiology, including the regulation of sleep, metabolism, and the immune system. Here, we review advances in understanding the genetic regulation of sleep through the circadian system, as well as the impact of dysregulated gene expression on metabolic function. We also review recent studies that have begun to unravel the circadian clock’s role in controlling the cardiovascular and nervous systems, gut microbiota, cancer, and aging. Such circadian control of these systems relies, in part, on transcriptional regulation, with recent evidence for genome-wide regulation of the clock through circadian chromosome organization. These novel insights into the genomic regulation of human physiology provide opportunities for the discovery of improved treatment strategies and new understanding of the biological underpinnings of human disease.

scholarly journals Minireview: The Circadian Clockwork of the Suprachiasmatic Nuclei—Analysis of a Cellular Oscillator that Drives Endocrine Rhythms

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5624-5634 ◽  
Author(s):  
Elizabeth S. Maywood ◽  
John S. O’Neill ◽  
Johanna E. Chesham ◽  
Michael H. Hastings
Keyword(s):  
Neural Circuits ◽  
Clock Genes ◽  
Time Base ◽  
Suprachiasmatic Nuclei ◽  
Dark Cycle ◽  
Cellular Mechanisms ◽  
Circadian Control ◽  
Daily Cycles ◽  
Central Clock ◽  
Retinal Afferents

The secretion of hormones is temporally precise and periodic, oscillating over hours, days, and months. The circadian timekeeper within the suprachiasmatic nuclei (SCN) is central to this coordination, modulating the frequency of pulsatile release, maintaining daily cycles of secretion, and defining the time base for longer-term rhythms. This central clock is driven by cell-autonomous, transcriptional/posttranslational feedback loops incorporating Period (Per) and other clock genes. SCN neurons exist, however, within neural circuits, and an unresolved question is how SCN clock cells interact. By monitoring the SCN molecular clockwork using fluorescence and bioluminescence videomicroscopy of organotypic slices from mPer1::GFP and mPer1::luciferase transgenic mice, we show that interneuronal neuropeptidergic signaling via the vasoactive intestinal peptide (VIP)/PACAP2 (VPAC2) receptor for VIP (an abundant SCN neuropeptide) is necessary to maintain both the amplitude and the synchrony of clock cells in the SCN. Acute induction of mPer1 by light is, however, independent of VIP/VPAC2 signaling, demonstrating dissociation between cellular mechanisms mediating circadian control of the clockwork and those mediating its retinally dependent entrainment to the light/dark cycle. The latter likely involves the Ca2+/cAMP response elements of mPer genes, triggered by a MAPK cascade activated by retinal afferents to the SCN. In the absence of VPAC2 signaling, however, this cascade is inappropriately responsive to light during circadian daytime. Hence VPAC2-mediated signaling sustains the SCN cellular clockwork and is necessary both for interneuronal synchronization and appropriate entrainment to the light/dark cycle. In its absence, behavioral and endocrine rhythms are severely compromised.

Eating breakfast and avoiding the evening snack sustains lipid oxidation

2020 ◽  
Author(s):  
Kevin Parsons Kelly ◽  
Owen P. McGuinness ◽  
Maciej Buchowski ◽  
Jacob J. Hughey ◽  
Heidi Chen ◽  
...  
Keyword(s):  
Lipid Oxidation ◽  
Eating Habits ◽  
Core Body Temperature ◽  
Daily Cycle ◽  
Meal Timing ◽  
Circadian Control ◽  
Late Evening ◽  
Older Subjects ◽  
Random Crossover ◽  
Core Body

SUMMARYCircadian (daily) regulation of metabolic pathways implies that food may be metabolized differentially over the daily cycle. To test that hypothesis, we monitored the metabolism of older subjects in a whole-room respiratory chamber over two separate 56-h sessions in a random crossover design. In one session, one of the three daily meals was presented as breakfast whereas in the other session, a nutritionally equivalent meal was presented as a late-evening snack. The duration of the overnight fast was the same for both sessions. Whereas the two sessions did not differ in overall energy expenditure, the respiratory exchange ratio (RER) was different during sleep between the two sessions. Unexpectedly, this difference in RER due to daily meal timing was not due to daily differences in physical activity, sleep disruption, or core body temperature. Rather, we found that the daily timing of nutrient availability coupled with daily/circadian control of metabolism drives a switch in substrate preference such that the late-evening snack session resulted in significantly lower lipid oxidation compared to the breakfast session. Therefore, the timing of meals during the day/night cycle affects how ingested food is oxidized or stored in humans with important implications for optimal eating habits.

scholarly journals Circadian Control of Kisspeptin and a Gated GnRH Response Mediate the Preovulatory Luteinizing Hormone Surge

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 595-606 ◽  
Author(s):  
Wilbur P. Williams ◽  
Stephan G. Jarjisian ◽  
Jens D. Mikkelsen ◽  
Lance J. Kriegsfeld
Keyword(s):  
Neural Circuit ◽  
Time Of Day ◽  
Circadian System ◽  
Cellular Activity ◽  
Lh Surge ◽  
Gating Mechanism ◽  
Circadian Control ◽  
Maximal Sensitivity ◽  
Luteinizing Hormone Surge ◽  
Daily Changes

Abstract In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the day of proestrus by a timed, stimulatory signal originating from the circadian clock in the suprachiasmatic nucleus (SCN). The present studies explored whether kisspeptin is part of the essential neural circuit linking the SCN to the GnRH system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus). Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular activity consistent with a role in the circadian control of the LH surge. The SCN targets kisspeptin neurons via vasopressinergic (AVP), but not vasoactive intestinal polypeptide-ergic, projections. Because AVP administration can only stimulate the LH surge during a restricted time of day, we examined the possibility that the response to AVP is gated at the level of kisspeptin and/or GnRH neurons. Kisspeptin and GnRH activation were assessed after the administration of AVP during the morning (when AVP is incapable of initiating the LH surge) and the afternoon (when AVP injections stimulate the LH surge). Kisspeptin, but not GnRH, cellular activity was up-regulated after morning injections of AVP, suggesting that time-dependent sensitivity to SCN signaling is gated within GnRH but not kisspeptin neurons. In support of this possibility, we found that the GnRH system exhibits pronounced daily changes in sensitivity to kisspeptin stimulation, with maximal sensitivity in the afternoon. Together these studies reveal a novel mechanism of ovulatory control with interactions among the circadian system, kisspeptin signaling, and a GnRH gating mechanism of control.

The tides of human consciousness: descriptions and questions

1982 ◽  
Vol 242 (3) ◽  
pp. R163-R166
Author(s):  
A. T. Winfree
Keyword(s):  
New York ◽  
Mathematical Biology ◽  
Experimental Test ◽  
Mathematical Description ◽  
Circadian System ◽  
Human Consciousness ◽  
Sleep Timing ◽  
Rosetta Stone ◽  
Temperature Rhythm

A Rosetta Stone has appeared in our midst in the form of R. A. Wever's monograph The Circadian System of Man (New York: Springer-Verlag, 1979), describing the results of 20 years' experiments with J. Aschoff. In the January 1982 issue of this journal, Kronauer, Czeisler, Pilato, Moore-Ede, and Weitzman offer their decipherment: a mathematical description of man's circadian temperature rhythm and sleep timing based on their own experimental observations in the Bronx, confirming and substantially extending Wever's in Bavaria. This paper might have been as happily received by the Journal of Mathematical Biology or Biological Cybernetics. Accordingly I here attempt to disentangle numerical description from physiological hypothesis, emphasizing items that seem, at least in principle, susceptible to experimental test.

The neural circadian system of mammals

2011 ◽  
Vol 49 ◽  
pp. 1-17 ◽  
Author(s):  
Hugh D. Piggins ◽  
Clare Guilding
Keyword(s):  
Circadian Rhythms ◽  
Circadian System ◽  
Daily Activities ◽  
Suprachiasmatic Nuclei ◽  
Dark Cycle ◽  
Environmental Light ◽  
Endogenous Clock ◽  
Central Clock

Humans and other mammals exhibit a remarkable array of cyclical changes in physiology and behaviour. These are often synchronized to the changing environmental light–dark cycle and persist in constant conditions. Such circadian rhythms are controlled by an endogenous clock, located in the suprachiasmatic nuclei of the hypothalamus. This structure and its cells have unique properties, and some of these are reviewed to highlight how this central clock controls and sculpts our daily activities.

scholarly journals Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Zohar Ben-Moshe ◽  
Nicholas S. Foulkes ◽  
Yoav Gothilf
Keyword(s):  
Pineal Gland ◽  
Circadian Clock ◽  
Rapid Development ◽  
Model Organism ◽  
Circadian System ◽  
Zebrafish Model ◽  
Peripheral Oscillators ◽  
Clock Gene Expression ◽  
Functional Development ◽  
Central Clock

The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model.

Compensatory sleep response to 12 h wakefulness in young and old rats

2000 ◽  
Vol 278 (1) ◽  
pp. R125-R133 ◽  
Author(s):  
Priyattam J. Shiromani ◽  
Jun Lu ◽  
Dean Wagner ◽  
Jolleyin Thakkar ◽  
Mary Ann Greco ◽  
...  
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Slow Wave Sleep ◽  
The Elderly ◽  
Sprague Dawley ◽  
Night Sleep ◽  
Sleep Drive ◽  
Old Rats ◽  
F344 Rats ◽  
Homeostatic Mechanisms ◽  
Elderly Humans

There is a pronounced decline in sleep with age. Diminished output from the circadian oscillator, the suprachiasmatic nucleus, might play a role, because there is a decrease in the amplitude of the day-night sleep rhythm in the elderly. However, sleep is also regulated by homeostatic mechanisms that build sleep drive during wakefulness, and a decline in these mechanisms could also decrease sleep. Because this question has never been addressed in old animals, the present study examined the effects of 12 h wakefulness on compensatory sleep response in young (3.5 mo) and old (21.5 mo) Sprague-Dawley and F344 rats. Old rats in both strains had a diminished compensatory increase in slow-wave sleep (SWS) after 12 h of wakefulness (0700–1900, light-on period) compared with the young rats. In contrast, compensatory REM sleep rebound was unaffected by age. To assess whether the reduced SWS rebound in old rats might result from loss of neurons implicated in sleep generation, we counted the number of c-Fos immunoreactive (c-Fos-ir) cells in the ventral lateral preoptic (VLPO) area and found no differences between young and old rats. These findings indicate that old rats, similar to elderly humans, demonstrate less sleep after prolonged wakefulness. The findings also indicate that although old rats have a decline in sleep, this cannot be attributed to loss of VLPO neurons implicated in sleep.

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