Insect circadian rhythms and photoperiodism

Two clock-controlled processes, overt circadian rhythmicity and the photoperiodic induction of diapause, are described in the blow fly,Calliphora vicina and the fruit fly,Drosophila melanogaster. Circadian locomotor rhythms of the adult flies reflect endogenous, self-sustained oscillations with a temperature compensated period. The free-running rhythms become synchronised (entrained) to daily light:dark cycles, but become arrhythmic in constant light above a certain intensity. Some flies show fragmented rhythms (internal desynchronisation) suggesting that overt rhythmicity is the product of a multioscillator (multicellular) system. Photoperiodic induction of larval diapause inC. vicina and of ovarian diapause inD. melanogaster is also based on the circadian system but seems, to involve a separate mechanism at both the molecular and neuronal levels. For both processes in both species, the compound eyes and ocelli are neither essential nor necessary for photic entrainment, and the circadian clock mechanism is not within the optic lobes. The central brain is the most likely site for both rhythm generation and extra-optic photoreception. InD. melanogaster, a group of lateral brain neurons has been identified as important circadian pacemaker cells, which are possibly also photo-sensitive. Similar lateral brain neurons, staining for arrestin, a protein in the phototransduction ‘cascade’ and a selective marker for photoreceptors in both vertebrates and invertebrates, have been identified inC. vicina. Much less is known about the cellular substrate of the photoperiodic mechanism, but this may involve thepars intercerebralis region of the mid-brain.     

Insect photoperiodism: seeing the light

This review examines the spectral sensitivities of photoperiodic responses in insects and mites in relation to circadian‐based models for the photoperiodic clock. It concludes that there are probably a number of different photoreceptors at both the organ and molecular levels. These latter probably fall into two classes: (i) a blue‐light sensitive photoreceptor and (ii) a range of opsins (i.e. opsin proteins conjugated with a vitamin A based pigment) absorbing light at a range of wavelengths. In flesh flies (Sarcophaga spp. and possibly other higher Diptera), which are considered to exemplify the ‘external coincidence’ model, entrainment of the photoperiodic oscillator probably involves a blue‐light photoreceptor of Drosophila‐type CRYPTOCHROME (CRY1) absorbing maximally at approximately 470 nm, whereas opsins absorbing at longer wavelengths may be involved in the photo‐inductive process (diapause/nondiapause regulation) that occurs when dawn light coincides with the photo‐inducible phase. In the parasitic wasp Nasonia vitripennis, on the other hand, a species that lacks CRY1 but expresses the nonphotosensitive ‘mammalian‐type’ CRY2, and is considered to exemplify ‘internal coincidence’, entrainment of the dawn and dusk oscillators may involve opsin‐based photoreceptors absorbing light at longer wavelengths as far as the red end of the spectrum. In the Lepidoptera, which express both CRY1 and CRY2, properties of both external and internal coincidence may be evident. The presence or absence of cry1 in the genome may thus emerge as a key to the photoperiodic mechanism on its light input pathway.     

Feeding and circadian clocks

The mammalian genome encodes at least a dozen of genes directly involved in the regulation of the feedback loops constituting the circadian clock. The circadian system is built up on a multitude of oscillators organized according to a hierarchical model in which neurons of the suprachiasmatic nuclei of the hypothalamus may drive the central circadian clock and all the other somatic cells may possess the molecular components allowing tissues and organs to constitute peripheral clocks. Suprachiasmatic neurons are driving the central circadian clock which is reset by lighting cues captured and integrated by the melanopsin cells of the retina and define the daily rhythms of locomotor activity and associated physiological regulatory pathways like feeding and metabolism. This central clock entrains peripheral clocks which can be synchronized by non-photic environmental cues and uncoupled from the central one depending on the nature and the strength of the circadian signal. The human circadian clock and its functioning in central or peripheral tissues are currently being explored to increase the therapeutic efficacy of timed administration of drugs or radiation, and to offer better advice on lighting and meal timing useful for frequent travelers suffering from jet lag and for night workers' comfort. However, the molecular mechanism driving and coordinating the central and peripheral clocks through a wide range of synchronizers (lighting, feeding, physical or social activities) remains a mystery.     

What do mathematical models tell us about circadian clocks?

The paper reviews a series of models for circadian clocks and discusses their conclusions and predictions. Attention is focused on Pittendrigh's empirical model, two mathematical models by the author and Winfree's work.     

A model for circadian clocks

An extension of an earlier model simulating the effects of light on the drosophila eclosion rhythm is presented. The effects of variable light intensity are described. This allows not only the simulation of certain experiments not covered by the earlier model, but also it permits an extension of the model to other organisms. By changing only its sensitivity to light the model simulates the phase response curves of certain mammals as well as Aschoff’srule.     

Temperature effects on circadian clocks

Periodic temperature changes represent one of the most effective entraining (Zeitgeber) signals for circadian clocks in many organisms. Different constant temperatures affect the circadian amplitude and ultimately the expression of circadian clocks, while the circadian period length (tau) remains approximately constant (temperature compensation). Experimental results and theoretical models are presented that may serve to explain these effects. After introducing the physico-chemical basis of temperature on enzyme-catalyzed and physiological reactions, and after describing mechanisms for temperature adaptation of physiological reactions to different thermal environments, general effects of temperature on chemical and biological oscillators are described. Kinetic models for circadian clocks and temperature compensation are presented and compared with experimental results. Special attention is given to the question how constant but different temperature levels affect clock amplitude, period length and phase. Influences of single and periodic temperature variations (steps or pulses) on circadian clocks are presented together with models which may explain the resulting phase response curves and entrainment patterns. Because temperature compensation is only one aspect of a general homeostatic mechanism that keeps the circadian period rather constant, the influence of other environmental variables and their relationship to temperature are discussed.     

Adaptive significance of circadian clocks

Circadian clocks are ubiquitous and are found in organisms ranging from bacteria to mammals. This ubiquity of occurrence implies adaptive significance, but to date there has been no rigorous empirical evidence to support this. It is believed that an organism possessing circadian clocks gains fitness advantage in two ways: (i) by synchronizing its behavioral and physiological processes to cyclic environmental factors (extrinsic adaptive value); (ii) by coordinating its internal metabolic processes (intrinsic adaptive value). There is preliminary circumstantial evidence to support both. Several studies using organisms living in constant environments have shown that these organisms possess functional circadian clocks, suggesting that circadian clocks may have some intrinsic adaptive value. Studies to assess the adaptive value of circadian clocks in periodic environments suggest that organisms may have a fitness advantage in those periodic environments, which closely match their own intrinsic periodicity. Furthermore, evidence from organisms living in the wild, selection studies, and studies on latitudinal clines suggest that circadian clocks may have an extrinsic adaptive value as well. In this paper, I have presented several hypotheses for the emergence of circadian clocks and have reviewed some major empirical studies suggesting adaptive significance of circadian clocks.     

Riding tandem: circadian clocks and the cell cycle

The circadian clock, which governs metabolic and physiological rhythms in diverse organisms, shares common features with the cell cycle. Yet, these two oscillatory systems seem to be fully independent of each other. Recent studies now reveal that some essential regulatory elements are common to both the cell cycle and circadian clock.     

Temporal orientation: circadian clocks in animals and humans

By evolutionary adaptation to the regular day-night changes in environmental conditions, most organisms have acquired a temporal programme which matches the 24-h day. It rests on periodic processes which have the characteristics of self-sustaining oscillations, and which, in constant conditions, free-run with periods slightly deviating from 24 h. When entrained to 24 h, these circadian rhythms can be used by the organism as a clock for temporal orientation, e.g. in the occupation of one of the temporal niches provided by the environment or in the coordination of activities among individuals and species. The circadian clock also provides the basis for using the sun as a compass in spatial orientation, and for the recognition of the time of day as exemplified by the time sense in honey bees. Within the human organism, almost every function is modulated in a circadian fashion. Usually, all rhythms keep a distinct phase-relationship t to each other, providing a high degree of temporal order within the organism. When living in an isolation unit without time cues, most subjects develop free-running rhythms with periods close to 25 h in all functions. Sometimes, however, the sleep-wake cycle is lengthened to 30 h and more, or shortened to less than 22 h. In those instances, other rhythms such as that of body temperature become uncoupled from the sleep-wake cycle and continue to free-run with a period of about 25 h. During such states of ‘internal desynchronization’, subjects can be awake continuously for about 32 h, and sleep without interruption for 16 h. Nevertheless, they experience their ‘days’ as equal to 24 h. This is due to a profound change in time estimation: the intervals of 1-h estimates made by the subject are positively correlated with the duration of wakefulness. In contrast, short-time estimates (in the range of seconds) remain unaffected by desynchronization, indicating that short- and long-time estimates are based on different mechanisms.     

Cellular clocks: coupled circadian and cell division cycles

Gating of cell division by the circadian clock is well known, yet its mechanism is little understood. Genetically tractable model systems have led to new hypotheses and questions concerning the coupling of these two cellular cycles.     

Insect photoperiodism — the clock and the counter: a review

ABSTRACT. Insect photoperiodic responses are complex and variable, but all involve a 'clock' which is used to determine the qualitative difference between long and short nights, and a 'counter' mechanism which accumulates successive long (or short) nights quantitatively up to an internal threshold at which induction (of diapause, seasonal morphs, etc.) is 'complete'. The clock is circadianbased in at least seven species; in others a non-oscillatory 'hour-glass' device is indicated, but negative 'resonance' experiments may not necessarily rule out a circadian involvement in time measurement. The counter is temperature-compensated. In some species it adds up long nights, in some short nights, and in others long and short nights. The proportion of the population entering diapause is dependent on an interaction between the temperature-compensated counter and temperature-dependent rates of development; this interaction explains many of the known effects of temperature, diet, and latitude in insect photoperiodic responses. In formal terms, the accumulation of long nights is seen as an increase in a 'diapause titre' which is compared with an individual internal threshold. In concrete terms, this 'titre', and the counter mechanism, might be represented by the accumulation of neurosecretory granules within the neuro-endocrine system.