Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice.

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep-wake disturbances. The nychthemeral sleep-wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light-dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light-dark alternations exert direct and acute influences on sleep and waking.

Hepatic gene therapy rescues high-fat diet responses in circadian mutant mice.

Objective: Circadian gene mutant mice show dampened 24-h feeding rhythms and an increased sensitivity to high-fat diet (HFD) feeding. Restricting HFD access to the dark phase counteracts its obesogenic effect in wild-type mice. The extent to which altered feeding rhythms are causative for the obesogenic phenotype of mutant mice, however, remains unknown.

Tissue-Specific Dissociation of Diurnal Transcriptome Rhythms During Sleep Restriction in Mice.

Study Objectives: Shortened or mistimed sleep affects metabolic homeostasis, which may in part be mediated by dysregulation of endogenous circadian clocks. In this study, we assessed the contribution of sleep disruption to metabolic dysregulation by analysing diurnal transcriptome regulation in metabolic tissues of mice subjected to a sleep restriction (SR) paradigm.

Methods: Male mice were subjected to 2 × 5 days of SR with enforced waking during the first 6 hours of the light phase.

The SCN Clock Governs Circadian Transcription Rhythms in Murine Epididymal White Adipose Tissue.

The circadian master pacemaker in the suprachiasmatic nucleus (SCN) orchestrates peripheral clocks in various organs and synchronizes them with external time, including those in adipose tissue, which displays circadian oscillations in various metabolic and endocrine outputs. Because our knowledge about the instructive role of the SCN clock on peripheral tissue function is based mainly on SCN lesion studies, we here used an alternative strategy employing the Cre/ loxP system to functionally delete the SCN clock in mice. We performed whole-genome microarray hybridizations of murine epididymal white adipose tissue (eWAT) RNA preparations to characterize the role of the SCN clock in eWAT circadian transcriptome regulation.

Synchronization of the mammalian circadian timing system: Light can control peripheral clocks independently of the SCN clock: alternate routes of entrainment optimize the alignment of the body's circadian clock network with external time.

A vast network of cellular circadian clocks regulates 24-hour rhythms of behavior and physiology in mammals. Complex environments are characterized by multiple, and often conflicting time signals demanding flexible mechanisms of adaptation of endogenous rhythms to external time. Traditionally this process of circadian entrainment has been conceptualized in a hierarchical scheme with a light-reset master pacemaker residing in the hypothalamus that subsequently aligns subordinate peripheral clocks with each other and with external time.

The light-dark cycle controls peripheral rhythmicity in mice with a genetically ablated suprachiasmatic nucleus clock.

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN), which is thought to synchronize peripheral clocks in various organs with each other and with external time. Our knowledge about the role of the SCN clock is based mainly on SCN lesion and transplantation studies. We have now directly deleted the SCN clock using the Cre/LoxP system and investigated how this affects synchronization of peripheral rhythms.

Patterns across multiple memories are identified over time.

Memories are not static but continue to be processed after encoding. This is thought to allow the integration of related episodes via the identification of patterns. Although this idea lies at the heart of contemporary theories of systems consolidation, it has yet to be demonstrated experimentally.

Impaired glucocorticoid production and response to stress in Arntl-deficient male mice.

The basic helix-loop-helix transcription factor Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL, also known as BMAL1 or MOP3) is a core component of the circadian timing system in mammals, which orchestrates 24-hour rhythms of physiology and behavior. Genetic ablation of Arntl in mice leads to behavioral and physiological arrhythmicity, including loss of circadian baseline regulation of glucocorticoids (GCs). GCs are important downstream regulators of circadian tissue clocks and have essential functions in the physiological adaptation to stress.

Circadian regulation of adipose function.

Adipose physiology shows prominent variation over the course of the day, responding to changing demands in energy metabolism. In the last years the tight interaction between the endogenous circadian timing system and metabolic function has been increasingly acknowledged. Recent work suggests that clock and adipose function go hand in hand, regulating each other to ensure optimal adaptation to environmental changes over the 24-h cycle.

Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes.

Circadian desynchrony promotes metabolic disruption in a mouse model of shiftwork.

Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork.

Synaptotagmin10-Cre, a driver to disrupt clock genes in the SCN.

Surgical lesion of the suprachiasmatic nuclei (SCN) profoundly affects the circadian timing system. A complication of SCN ablations is the concomitant scission of SCN afferents and efferents. Genetic disruption of the molecular clockwork in the SCN provides a complementary, less invasive experimental approach.

Adrenal glucocorticoids as a target for jet lag therapies.

When traveling across time zones, our physiological functions lose synchrony relative to the external day. The endogenous circadian clocks that usually prepare our body for times of eating, sleeping and other rhythmic behavioral and physiological processes become temporally disrupted. Owing to the fact that these clocks cannot immediately realign, we experience jet lag, which is characterized by multiple physiological and psychological symptoms.

Innate attractiveness and associative learnability of odors can be dissociated in larval Drosophila.

We investigate olfactory associative learning in larval Drosophila. A reciprocal training design is used, such that one group of animals receives a reward in the presence of odor X but not in the presence of odor Y (Train: X+ // Y), whereas another group is trained reciprocally (Train: X // Y+). After training, differences in odor preference between these reciprocally trained groups in a choice test (Test: X - Y) reflect associative learning.

A time to fast, a time to feast: the crosstalk between metabolism and the circadian clock.

The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease.