Resetting the circadian clock by social experience in Drosophila melanogaster

Circadian clocks are influenced by social interactions in a variety of species, but little is known about the sensory mechanisms underlying these effects. We investigated whether social cues could reset circadian rhythms in Drosophila melanogaster by addressing two questions: Is there a social influence on circadian timing? If so, then how is that influence communicated? The experiments show that in a social context Drosophila transmit and receive cues that influence circadian time and that these cues are likely olfactory.     

Searching for genes underlying behavior: lessons from circadian rhythms

The success of forward genetic (from phenotype to gene) approaches to uncover genes that drive the molecular mechanism of circadian clocks and control circadian behavior has been unprecedented. Links among genes, cells, neural circuits, and circadian behavior have been uncovered in the Drosophila and mammalian systems, demonstrating the feasibility of finding single genes that have major effects on behavior. Why was this approach so successful in the elucidation of circadian rhythms? This article explores the answers to this question and describes how the methods used successfully for identifying the molecular basis of circadian rhythms can be applied to other behaviors such as anxiety, addiction, and learning and memory.     

哺乳动物生物钟昼夜节律同步机制的研究进展

哺乳动物昼夜节律生物钟是以24 h为周期的自主维持的振荡器。在分子水平上,生物钟的振荡由自身调控反馈环路的转录和翻译组成,并接受外界环境因素的影响,通过下丘脑视叉上核(Supra Ch iasm atic N u-cleus,SCN)中枢震荡器的同步整和而产生作用。文章对生物钟上下游的分布、反馈环路的转录、翻译后事件、视觉通路、钟的整和等方面进行了综述,并对其今后的研究方向作了展望。     

JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS

Organisms ranging from bacteria to humans synchronize their internal clocks to daily cycles of light and dark. Photic entrainment of the Drosophila clock is mediated by proteasomal degradation of the clock protein TIMELESS (TIM). We have identified mutations in jetlag-a gene coding for an F-box protein with leucine-rich repeats-that result in reduced light sensitivity of the circadian clock. Mutant flies show rhythmic behavior in constant light, reduced phase shifts in response to light pulses, and reduced light-dependent degradation of TIM. Expression of JET along with the circadian photoreceptor cryptochrome (CRY) in cultured S2R cells confers light-dependent degradation onto TIM, thereby reconstituting the acute response + of the circadian clock to light in a cell culture system. Our results suggest that JET is essential for resetting the clock by transmitting light signals from CRY to TIM.     

Regulation of circadian rhythmicity

Daily rhythms in many behavioral, physiological, and biochemical functions are generated by endogenous oscillators that function as internal 24-hour clocks. Under natural conditions, these oscillators are synchronized to the daily environmental cycle of light and darkness. Recent advances in locating circadian pacemakers in the brain and in establishing model systems promise to shed light on the cellular and biochemical mechanisms involved in the generation and regulation of circadian rhythms.     

Temperature as a universal resetting cue for mammalian circadian oscillators

Environmental temperature cycles are a universal entraining cue for all circadian systems at the organismal level with the exception of homeothermic vertebrates. We report here that resistance to temperature entrainment is a property of the suprachiasmatic nucleus (SCN) network and is not a cell-autonomous property of mammalian clocks. This differential sensitivity to temperature allows the SCN to drive circadian rhythms in body temperature, which can then act as a universal cue for the entrainment of cell-autonomous oscillators throughout the body. Pharmacological experiments show that network interactions in the SCN are required for temperature resistance and that the heat shock pathway is integral to temperature resetting and temperature compensation in mammalian cells. These results suggest that the evolutionarily ancient temperature resetting response can be used in homeothermic animals to enhance internal circadian synchronization.     

Action spectra for phase shifts of a circadian rhythm in Drosophila

Action spectra were determined for lightinduced phase shifts of the circadian rhythm of adult emergence in Drosophila pseudoobscura. The action spectra for advance and delay phase shifts are similar; the most effective wavelengths are in the blue region, with a sharp cutoff above 500 nanometers. This similarity suggests that the same photoreceptive pigment mediates both advance and delay phase shifts.     

Circadian integration of metabolism and energetics

Circadian clocks align behavioral and biochemical processes with the day/night cycle. Nearly all vertebrate cells possess self-sustained clocks that couple endogenous rhythms with changes in cellular environment. Genetic disruption of clock genes in mice perturbs metabolic functions of specific tissues at distinct phases of the sleep/wake cycle. Circadian desynchrony, a characteristic of shift work and sleep disruption in humans, also leads to metabolic pathologies. Here, we review advances in understanding the interrelationship among circadian disruption, sleep deprivation, obesity, and diabetes and implications for rational therapeutics for these conditions.     

Mapping the core of the Arabidopsis circadian clock defines the network structure of the oscillator

In many organisms, the circadian clock is composed of functionally coupled morning and evening oscillators. In Arabidopsis, oscillator coupling relies on a core loop in which the evening oscillator component TIMING OF CAB EXPRESSION 1 (TOC1) was proposed to activate a subset of morning-expressed oscillator genes. Here, we show that TOC1 does not function as an activator but rather as a general repressor of oscillator gene expression. Repression occurs through TOC1 rhythmic association to the promoters of the oscillator genes. Hormone-dependent induction of TOC1 and analysis of RNA interference plants show that TOC1 prevents the activation of morning-expressed genes at night. Our study overturns the prevailing model of the Arabidopsis circadian clock, showing that the morning and evening oscillator loops are connected through the repressing activity of TOC1.     

Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage

Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long- and short-circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.