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In this review, we provide a summary of the field of mammalian circadian neurobiology circa 2015. While many additional details have emerged in the intervening 7 years, understanding of the fundamental structure and function of this critical neural system remains intact. Thus, the present review continues to provide a valuable introduction for those seeking an integrative multilevel overview of the circadian system. In brief, the circadian system comprises a coupled network of molecular/cellular- and tissue-level oscillators, hierarchically coordinated by the hypothalamic suprachiasmatic nuclear circadian pacemaker, and entrained by both photic and nonphotic signals., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Chrononutrition is an emerging discipline that builds on the intimate relation between endogenous circadian (24-h) rhythms and metabolism. Circadian regulation of metabolic function can be observed from the level of intracellular biochemistry to whole-organism physiology and even postprandial responses. Recent work has elucidated the metabolic roles of circadian clocks in key metabolic tissues, including liver, pancreas, white adipose, and skeletal muscle. For example, tissue-specific clock disruption in a single peripheral organ can cause obesity or disruption of whole-organism glucose homeostasis. This review explains mechanistic insights gained from transgenic animal studies and how these data are being translated into the study of human genetics and physiology. The principles of chrononutrition have already been demonstrated to improve human weight loss and are likely to benefit the health of individuals with metabolic disease, as well as of the general population., (© 2016 American Society for Nutrition.)

Over the past few decades, multilevel research has elucidated the basic neuroanatomy, neurochemistry, and molecular neurobiology of the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). The circadian timing system is composed of a large number of cellular oscillators located in the SCN, in non-SCN brain structures, and throughout the body. Cellular-level oscillations are generated by a molecular feedback loop in which circadian clock genes rhythmically regulate their own transcription, as well as that of hundreds of clock-controlled genes. The maintenance of proper coordination within this network of cellular- and tissue-level clocks is essential for health and well-being., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Diurnal variations in the incidence of events such as heart attack and stroke suggest a role for circadian rhythms in the etiology of cardiovascular disease. The aim of this study was to assess the influence of the suprachiasmatic nucleus (SCN) circadian clock on cardiovascular function., Methodology/principal Findings: Heart rate (HR), blood pressure (BP) and locomotor activity (LA) were measured in circadian mutant (Vipr2(-/-)) mice and wild type littermates, using implanted radio-telemetry devices. Sleep and wakefulness were studied in similar mice implanted with electroencephalograph (EEG) electrodes. There was less diurnal variation in the frequency and duration of bouts of rest/activity and sleep/wake in Vipr2(-/-) mice than in wild type (WT) and short "ultradian" episodes of arousal were more prominent, especially in constant conditions (DD). Activity was an important determinant of circadian variation in BP and HR in animals of both genotypes; altered timing of episodes of activity and rest (as well as sleep and wakefulness) across the day accounted for most of the difference between Vipr2(-/-) mice and WT. However, there was also a modest circadian rhythm of resting HR and BP that was independent of LA., Conclusions/significance: If appropriate methods of analysis are used that take into account sleep and locomotor activity level, mice are a good model for understanding the contribution of circadian timing to cardiovascular function. Future studies of the influence of sleep and wakefulness on cardiovascular physiology may help to explain accumulating evidence linking disrupted sleep with cardiovascular disease in man.

In the female mouse, ovulation and estrous cyclicity are under both hormonal and circadian control. We have shown that mice with a mutation in the core circadian gene Clock have abnormal estrous cycles and do not have a luteinizing hormone (LH) surge on the afternoon of proestrus due to a defect at the hypothalamic level. In the present study, we tested the hypotheses that vasopressin (AVP) can act as a circadian signal to regulate the proestrous release of LH, and that this signal is deficient in the Clock mutant. We found that Avp expression in the suprachiasmatic nucleus (SCN) and AVP 1a receptor (Avpr1a) expression in the hypothalamus is reduced in Clock mutant mice compared to wild-type mice. Intracerebroventricular (i.c.v.) injection of AVP on the afternoon of proestrus is sufficient to induce LH secretion, which reaches surge levels in 50% of Clock mutant mice. The effect of AVP on the Clock mutant LH surge is mediated by AVPR1A, as co-infusion of AVP and an AVPR1A-specific antagonist prevents AVP induction of LH release, although infusion of an AVPR1A antagonist into wild-type mice failed to prevent a proestrous LH surge. These results suggest that reduced hypothalamic AVP signaling plays a role in the absence of the proestrous LH surge in Clock mutant mice. The results also support the hypothesis that AVP produced by the SCN may be a circadian signal that regulates LH release.

Context: Sleep is regulated by circadian and homeostatic processes. The circadian pacemaker, located in the suprachiasmatic nuclei (SCN), regulates the timing and consolidation of the sleep-wake cycle, while a homeostatic mechanism governs the accumulation of sleep debt and sleep recovery. Recent studies using mice with deletions or mutations of circadian genes show that components of the circadian pacemaker can influence the total amount of baseline sleep and recovery from sleep deprivation, indicating a broader role for the SCN in sleep regulation., Objective: To further investigate the role of the circadian pacemaker in sleep regulation in mice, we recorded sleep in sham and SCN-lesioned mice under baseline conditions and following sleep deprivation., Results: Compared to sham controls, SCN-lesioned mice exhibited a decrease in sleep consolidation and a decrease in wakefulness during the dark phase. Following sleep deprivation, SCN-lesioned mice exhibited an attenuated increase in non-rapid eye movement sleep time but an increase in non-rapid eye movement sleep electroencephalographic delta power that was similar to that of the sham controls., Conclusions: These findings support the hypothesis that the SCN consolidate the sleep-wake cycle by generating a signal of arousal during the subjective night (ie. the active period), thereby having the capacity to alter baseline sleep amount. Although the SCN are not involved in sleep homeostasis as defined by the increase in electroencephalographic delta power after sleep deprivation, the SCN does play a central role in the regulation of sleep and wakefulness beyond just the timing of vigilance states.

The suprachiasmatic nuclei (SCN) of the hypothalamus are the site of the main circadian clock in mammals. Synchronization of the SCN to light is achieved by direct retinal inputs. The present study performed in rats transferred to constant darkness shows that blood glucose, pH and PCO2 display significant diurnal changes when measurements were made during the subjective day, the early subjective night or the late subjective night. The effects of a 30-min light exposure (100 lx) on these metabolic parameters at each of these circadian times were assessed. Regardless of the circadian time, light induced an increase in blood glucose, but did not affect plasma pH and PCO2. This study suggests that blood glucose, PCO2 and acid-base state are under circadian control, most likely mediated by the SCN, while the hyperglycemic response to light seems not to be gated by a circadian clock and may thus involve retinal inputs to non-SCN retino-recipient areas.

Circadian rhythm sleep disorders (CRSDs), whether chronic or transient, affect a broad range of individuals, including many elderly, those with severe visual impairments, shift workers, and jet travelers moving rapidly across many time zones. In addition, various forms of insomnia affect another large sector of the population. A feature common among CRSDs and some forms of insomnia is sensitivity to the hormone melatonin, which is secreted by the pineal gland. Accumulating evidence suggests that melatonin may regulate the circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the light–dark cycle is the primary signal that entrains the circadian clock to environmental cycles, exogenous melatonin has been shown to entrain the clock in individuals with no light perception and free-running circadian rhythms. Furthermore, studies have reported beneficial effects of melatonin for treatment of certain insomnias. Together, these studies suggest that melatonin may be useful for treating some insomnias and CRSDs. In these contexts, use of melatonin as a supplement has been popular in the United States. Unfortunately, the therapeutic potential of melatonin has been difficult to realize in clinical trials, possibly owing to non-specific actions of the agent and its unfavorable pharmacokinetic properties when administered orally. In an attempt to take advantage of the therapeutic opportunities available through the brain''s melatonin system, researchers have developed several melatonin agonists with improved properties in comparison to melatonin. Some of these agents are now in clinical trials for treatment of insomnia or CRSDs. [Copyright &y& Elsevier]

Determines if augmenting the amplitude of the rhythm of the endogenous molecule melatonin would augment the response of the circadian timing system of the hamster to a nonphotic phase-shifting agent, triazolam. Composition of the circadian timing system; Determination if the feeding regimen delivered a physiological or pharmacological dose of melatonin; Influence of melatonin on the activity of suprachiasmatic nuclei neurons.

1997 marks the 25th anniversary of the discovery of the master circadian pacemaker in mammals in the hypothalamic suprachiasmatic nucleus. Remarkable progress has been made over the last 25 years in elucidating the physiological mechanisms involved in the entrainment, generation and expression of circadian rhythms at the cellular and systems levels. The recent discovery and cloning of the first mammalian clock gene is expected to lead to rapid advances in the understanding of the genetic and molecular mechanisms underlying circadian rhythmicity in mammals. Indeed, the impressive and extensive database on circadian rhythms in mammals obtained over the past 25 years provides a foundation for making rapid progress in utilizing future genetic and molecular findings for discovering the fundamental mechanisms controlling 24-hour temporal organization. [ABSTRACT FROM AUTHOR]

Focuses on a series of studies which deal with biological rhythms. Factors which affect biological rhythms; Role of retinal hypothalamic trait (RHT) in the circadian rhythm; Functions of the suprachiasmatic nucleus; Details on the regulation of circadian rhythms.