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At least 487 records · Page 27Linked to original sources
PubMed2006

Encoding the ins and outs of circadian pacemaking.

The SCN of the mammalian hypothalamus comprises a self-sustained, biological clock that generates endogenous ca. 24-h (circadian) rhythms. Circadian rhythmicity in the SCN originates from the interaction of a defined set of "clock genes" that participate in transcription/translation feedback loops. In order for the SCN to serve as an internal clock that times an internal day corresponding to the external solar day, the intracellular molecular oscillations must be output as physiological signals and be reset by appropriate environmental inputs. Here, the authors consider the mechanisms by which the SCN circadian pacemaker encodes rhythmic output and light input. In particular, they focus on the ionic mechanisms by which SCN neurons encode clock gene output as circa-dian rhythms in spike frequency, as well as cellular and molecular mechanisms by which SCN neurons encode circadian light input through phase heterogeneity in the SCN network. The authors propose that there are 2 distinct classes of ionic mechanisms supporting spike frequency rhythms output--modulation of basal membrane potential and conductance versus modulation of spike production--whereas light input is transformed by cellular communication within the SCN network and encoded by the relative phase relationships among SCN neurons.

Action Potentials↗
PubMed2005

Circadian organization in reindeer.

The light/dark cycle of day and night synchronizes an internal 'biological clock' that governs daily rhythms in behaviour, but this form of regulation is denied to polar animals for most of the year. Here we demonstrate that the continuous lighting conditions of summer and of winter at high latitudes cause a loss in daily rhythmic activity in reindeer living far above the Arctic Circle. This seasonal absence of circadian rhythmicity may be a ubiquitous trait among resident polar vertebrates.

Animals↗
PubMed1992

Neurotransmitters and the pharmacology of the suprachiasmatic nuclei.

The suprachiasmatic nucleus is the major component of the biological clock responsible for the generation and the regulation of circadian rhythms in behavioral and physiological functions. The SCN acts as an endogenous circadian pacemaker that becomes entrained to the light/dark cycle. Although many neuropeptides and neurotransmitters have been localized within and around the SCN, their role in the generation of the circadian signal still has to be elucidated. There are some data about the transmitters that are involved in the mechanism of entrainment. The way the SCN modulates the homeostatic control systems that are involved in the control of behaviour, also needs more clarification.

Animals↗
PubMed2005

Seasonal fluctuations of glial fibrillary acidic protein (GFAP) immunoreactivity in the rat suprachiasmatic nucleus.

The pacemaker of the "biological clock", the suprachiasmatic nucleus (SCN) of the hypothalamus was studied in intact male rats for glial fibrillary acidic protein (GFAP) a specific marker for astrocytes. Immunohistochemical reactions were carried out in winter (January-February) and in summer (June-July). In winter the GFAP-immunoreactivity of the SCN was found low whereas in summer it was high. Gonadectomy reduced differences. Since photic stimuli that apparently trigger the observed differences reach the SCN through identified neuronal pathways we conluded that the reaction of astrocytes is an indicator of seasonally altered neuronal function in the SCN.

Animals↗
PubMed2003

Peripheral circadian oscillators and their rhythmic regulation.

Most of the organisms living on earth show 24 hour (circadian) rhythms that are endogenously controlled by biological clocks. In mammals, these rhythms are generated by the circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. However, recent studies have demonstrated that circadian oscillators can be found in many organs and tissues, and it appears that the circadian oscillators in the periphery are not self-sustained, since, in vitro, the oscillation disappears after a few cycles. Although analysis of the clockwork mechanism indicates that the molecular composition of the clock in the SCN and in the peripheral tissues is very similar, the mechanism responsible for the damping of the circadian oscillation in the periphery is unknown. Recent studies have also indicated that the mammalian circadian system is hierarchically organized in that the SCN (i.e., the master circadian pacemaker) controls the peripheral oscillators in order to coordinate the physiological events in an entire body. The mechanisms by which the SCN controls peripheral oscillators are just starting to be elucidated. The aim of this review is to summarize the most recent findings on functioning of these extra-SCN oscillators and the mechanisms the SCN controls peripheral oscillators.

Animals↗
PubMed2005

Photoperiod-sensitive developmental delay in facet mutants of the drosophilid fly, Chymomyza costata and the genetic interaction with timeless.

Previously, we demonstrated that the biological clock gene, timeless (tim), is potentially involved in photoperiodic diapause induction in the larvae of the drosophilid fly Chymomyza costata. Suppression of tim transcription was inevitably associated with the loss of diapause induction even under diapause-promoting short-day conditions. In the present paper, I report a novel gene, facet (fa), which may genetically interact with tim in photoperiodically controlled larval development in this species. I demonstrated the effect of photoperiod on the development of fa morphological mutants. Developmental delay was remarkable in fa larvae under a diapause-preventing photoperiod, 16 h light: 8 h dark/day, in which the wild-type individuals showed normal and synchronous development. The delay was recovered by extension of the light phase of daily light/dark cycles or the introgression of a deficient tim allele.

Animals↗
PubMed2004

Visualizing a circadian clock protein: crystal structure of KaiC and functional insights.

Circadian (daily) biological clocks express characteristics that are difficult to explain by known biochemical mechanisms, and will ultimately require characterizing the structures, functions, and interactions of their molecular components. KaiC is an essential circadian protein in cyanobacteria that forms the core of the KaiABC clock protein complex. We report the crystal structure of the KaiC homohexameric complex at 2.8 A resolution. The structure resembles a double doughnut with a central pore that is partially sealed at one end. The crystal structure reveals ATP binding, inter-subunit organization, a scaffold for Kai-protein complex formation, the location of critical KaiC mutations, and evolutionary relationships to other proteins. A key auto-phosphorylation site on KaiC (T432) is identified from the crystal structure, and mutation of this residue abolishes circadian rhythmicity. The crystal structure of KaiC will be essential for understanding this circadian clockwork and for establishing its links to global gene expression.

Adenosine Triphosphate↗
PubMed1988

In situ localization of the per clock protein during development of Drosophila melanogaster.

The per locus influences biological rhythms in Drosophila melanogaster. In this study, per transcripts and proteins were localized in situ in pupae and adults. Earlier genetic studies have demonstrated that per expression is required in the brain for circadian locomotor activity rhythms and in the thorax for ultradian rhythmicity of the Drosophila courtship song. per RNA and proteins were detected in a restricted group of cells in the eyes and optic lobes of the adult brain and in many cell bodies in the adult and pupal thoracic ganglia. per products were also found in the pupal ring gland complex, a tissue involved in rhythmic aspects of Drosophila development. Abundant expression was seen in gonadal tissue. No biological clock phenotypes have been reported for this tissue in any of the per mutants, per protein mapped to different subcellular locations in different tissues. The protein accumulated in or around nuclei in some cells and appeared to be cytoplasmic in others.

Animals↗
PubMed1994

Pinopsin is a chicken pineal photoreceptive molecule.

In avian pinealocytes, an environmental light signal resets the phase of the endogenous circadian pacemaker that controls the rhythmic production of melatonin. Investigation of the pineal phototransduction pathway should therefore reveal the molecular mechanism of the biological clock. The presence of rhodopsin-like photoreceptive pigment, transducin-like immunoreaction, and cyclic GMP-dependent cation-channel activity in the avian pinealocytes suggests that there is a similarity between retinal rod cells and pinealocytes in the phototransduction pathway. We have now cloned chicken pineal cDNA encoding the photoreceptive molecule, which is 43-48% identical in amino-acid sequence to vertebrate retinal opsins. Pineal opsin, produced by transfection of complementary DNA into cultured cells, was reconstituted with 11-cis-retinal, resulting in formation of a blue-sensitive pigment (lambda max approximately 470 nm). In the light of this functional evidence and because the gene is specifically expressed only in the pineal gland, we conclude that it is a pineal photosensor and name it pinopsin.

Amino Acid Sequence↗
PubMed1989

[The effect of natural daylight on human regulation].

Day-light stimulates the endocrine glands about the biological clock. The annual variation of day-length and brightness lead to uni-modal annual rhythms of morbidity, mortality and physiological parameters too. Meteoropathological disturbances show an antagonistic influence of interdiurnal variations of day-light. In summer-time the seldom dark days and in winter-time the seldom bright days induce such phenomena. Another antagonistic influence of day-light is reflected by a bi-modal annual and by an about 14-days-rhythm. Upper-waves of annual rhythms with frequencies between 7 and 35 days can be synchronized by strong interdiurnal changes of day-light for man living in the same geographical region. The results as a whole may be explained by interdiurnal and seasonal modifications of human diurnal rhythms in form of changing phase-differences of two or more circadian oscillators.

Biological Clocks↗
PubMed2005

Headache due to photosensitive magnesium depletion.

Clinical and paraclinical data (visual stress tests, electroencephalographic and cerebrovascular photic driving, visual evoked potentials) demonstrate that the concept of photosensitive headache is fully justified. The interictal hallmark of photosensitive cephalalgic patients is potentiation (or sensitization) instead of habituation. The aetiopathogenic mechanisms of photosensitive headache associate hypofunction of the biological clock and magnesium depletion. The new concept of headache due to photosensitive magnesium depletion seems justified. It appears logical to add the treatments of magnesium depletion and of photosensitivity to classical treatment of headache. Prophylactic magnesium treatment relies on atoxic nutritional magnesium supplementation in case of primary magnesium deficiency. Pharmacological doses of parenteral magnesium may be used but may induce toxicity. Therefore it is necessary to know the therapeutic index of magnesium compound used: the larger its value, the greater the safety margin. Treatment of photosensitivity uses various types of < >: darkness therapy through physiologic, psychotherapic, physiotherapic, pharmacologic stimulating techniques and substitutive darkness therapy through palliative treatment. Melatonin is only a partial substitutive treatment of photosensitivity. A new model of photosensitive magnesium depletion with potentiation should be a useful tool for discriminating the most efficient gent.

Biological Clocks↗
PubMed1997

Newborn primate infants are entrained by low intensity lighting.

At the present time we do not know when the circadian timing system of human infants becomes responsive to light. Because of human study limitations, it is not currently possible to address this issue in clinical studies. Therefore, to provide insights into when the circadian system of humans becomes responsive to light, baboons were studied. We first assessed if the biological clock located in suprachiasmatic nuclei (SCN) is responsive to light at birth. When term newborn infants were exposed to bright light at night (5000 lux), SCN metabolic activity and c-fos mRNA expression increased, indicating the presence of photic responsiveness. When photic entrainment of developing rhythmicity was examined in infants, low intensity (200 lux) cycled lighting was sufficient to entrain circadian phase. However, low intensity lighting was not sufficient to induce changes in SCN metabolic activity or c-fos mRNA expression. Phase-response studies indicated that light exposure (200 lux) before the onset of activity most effectively shifted circadian phase. These data provide direct evidence that the SCN are responsive to visually mediated light information in a primate at birth. Further consideration of lighting conditions that infants are exposed to is therefore warranted.

Age Factors↗
PubMed1996

Circadian clock-controlled genes isolated from Neurospora crassa are late night- to early morning-specific.

An endogenous circadian biological clock controls the temporal aspects of life in most organisms, including rhythmic control of genes involved in clock output pathways. In the fungus Neurospora crassa, one pathway known to be under control of the clock is asexual spore (conidia) development. To understand more fully the processes that are regulated by the N. crassa circadian clock, systematic screens were carried out for genes that oscillate at the transcriptional level. Time-of-day-specific cDNA libraries were generated and used in differential screens to identify six new clock-controlled genes (ccgs). Transcripts specific for each of the ccgs preferentially accumulate during the late night to early morning, although they vary with respect to steady-state mRNA levels and amplitude of the rhythm. Sequencing of the ends of the new ccg cDNAs revealed that ccg-12 is identical to N. crassa cmt encoding copper metallothionein, providing the suggestion that not all clock-regulated genes in N. crassa are specifically involved in the development of conidia. This was supported by finding that half of the new ccgs, including cmt(ccg-12), are not transcriptionally induced by developmental or light signals. These data suggest a major role for the clock in the regulation of biological processes distinct from development.

Chromosome Mapping↗
PubMed1978

Ontogenesis of circadian rhythm of melatonin synthesis in pineal gland of rat.

Serotonin N-acetyltransferase (NAT) activity regulates the circadian rhythm of melatonin synthesis in pineal gland. NAT rhythm persisted in continuous darkness or in blinded rats. Development of the circadian rhythm of NAT activity was followed in the infant rats raised under various lighting schedules. The pups born and raised in continuous darkness or under constant illumination showed a rhythmic change indicating that the biological clock for NAT is generated inborn independent of environmental light-dark schedules. In the absence of light, the rhythms of pups synchronized with mother's rhythm. When rats were maintained under a ultradian light-dark schedule (LD 6:6), NAT activity showed a circadian change increasing once a day. When pups were born and raised under the ultradian lighting condition, NAT activity rhythm coincided with mother's rhythm. When pups were raised by a foster mother who had an inverted rhythm from that of an original mother, the rhythm of the pups synchronized with that of the foster mother. Whe pups were separated from their mother daily for 12 hours, their NAT rhythms reappeared when they were separated from their mother. These observations indicated a novel mechanism that in the absence of light-dark schedule, mothers taught the circadian rhythm to the pups as they raised them.

Acetyltransferases↗
PubMed1982

Pineal gland - pituitary (alpha-MSH) interrelationships in fur priming and reproductive cycles in mink (Mustela vison).

Our investigations show that blindness, either natural or surgically induced results in a lack of fur priming and sexual development. Definite genetic color phase differences were observed in the sensitivities of the biological clocks for initiating fur priming, testicular development and time of breeding and whelping. Finely-bred dark mink molted and their pelts primed later in the fall than did either pastel or opaline mink. Testicular development was earlier and more extensive for the opaline, but was intermediate for the pastels and slower and least extensive for the finely-bred dark mink. The dark mink, however, bred earlier than did either the pastel and opaline strains. Hedlund (deaf, white) mink pelted about the same time as the pastels and opalines, but they bred and whelped later than the above three strains of mink. Plasma alpha-MSH levels were inversely related to testosterone levels and testicular development. It was high in all three strains (darks, pastels and opalines) during both the spring and autumnal molts, but was low during testicular development and breeding.

Animals↗
PubMed2001

Behavioral responses to light in mice with dorsal lateral geniculate lesions.

Light has rapid direct effects on behavior and physiology that may be distinguished from its indirect effects that occur via synchronization of the biological clock. In nocturnal animals, light at night acutely suppresses the wheel running activity usually observed at that time of day. This is known as masking because light masks the overt expression of the circadian activity rhythm. In the present study, we compared the effects of light on wheel running in mice with bilateral electrolytic lesions of the dorsal lateral geniculate nucleus (DLG) to those in sham-operated animals. DLG-lesioned animals exhibited greater suppression of wheel running in response to bright light than did the controls, but failed to exhibit the increased activity in response to dim light observed in intact animals. These findings support the view that masking effects of light on behavior comprise two opposing processes, one that increases activity and is mediated by the classical visual system, and another that suppresses activity and is mediated by a non image-forming irradiance detection system.

Animals↗
PubMed1992

Melatonin influences Fos expression in the rat suprachiasmatic.

Administration of the pineal hormone melatonin to rats induces expression of Fos, the protein product of the c-fos proto-oncogene, in the suprachiasmatic nucleus (SCN), the putative biological clock of mammals. Expression of the Fos protein is dependent on circadian phase: injections in the late subjective night (circadian time (CT) 22) induce Fos expression in cells within the ventral SCN whereas injections during the subjective day are ineffective. Since melatonin injections in the late subjective day have previously been shown to phase advance circadian rhythms, these results indicate that phase-advances of the circadian system can occur without increased expression of Fos protein in the SCN, at least at levels detectable by immunohistochemistry. In support of in situ hybridization histochemical evidence obtained previously, immunocytochemical data from vehicle-injected control rats suggest that the Fos protein undergoes an endogenous fluctuation with peak levels in the SCN occurring during the subjective night. These observations indicate that melatonin can affect immediate early gene expression within the SCN.

Animals↗
PubMed2004

Blockade of GABAA receptors disrupts isoperiodic neuronal oscillations in the intergeniculate leaflet of the rat.

The intergeniculate leaflet of the thalamus is, besides the suprachiasmatic nucleus of the hypothalamus, the other important neuronal element of the mammalian biological clock. The extracellularly recorded activity of neurons constituting the intergeniculate leaflet, recorded in vivo, is characterized by distinct, very regular ultradian oscillations. The majority of neurons in the circadian timing system are GABAergic. Many, if not all, neurons of the suprachiasmatic nucleus and intergeniculate leaflet contain GABA. In the present study we examined the effects of the GABA(A) receptor antagonist bicuculline and the chloride channel blocker picrotoxin on isoperiodic neuronal oscillations in the intergeniculate leaflet of rats. We recorded extracellular multiple-unit neuronal activity from the intergeniculate leaflet of anesthetized rats. During the recording of isoperiodic oscillations, bicuculline or picrotoxin were stereotaxically injected at different concentrations into the lateral ventricle of rat brain. In all the experiments, injection of GABA(A) receptor antagonists transiently disrupted the isoperiodic phasic discharge recorded from the intergeniculate leaflet. These data suggest that GABA(A) receptors are involved in the generation of ultradian rhythmical neuronal oscillations in rat intergeniculate leaflet.

Action Potentials↗