Time in the biological sense is measured by cycles that range from milliseconds to years. Circadian rhythms, which measure time on a scale of 24 h, are generated by one of the most ubiquitous and well-studied timing systems. At the core of this timing mechanism is an intricate molecular mechanism that ticks away in many different tissues throughout the body. However, these independent rhythms are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.

Coordination of circadian timing in mammals

1980 Preface * 1999 Preface * 1999 Acknowledgements * Introduction * 1 Circular Logic * 2 Phase Singularities (Screwy Results of Circular Logic) * 3 The Rules of the Ring * 4 Ring Populations * 5 Getting Off the Ring * 6 Attracting Cycles and Isochrons * 7 Measuring the Trajectories of a Circadian Clock * 8 Populations of Attractor Cycle Oscillators * 9 Excitable Kinetics and Excitable Media * 10 The Varieties of Phaseless Experience: In Which the Geometrical Orderliness of Rhythmic Organization Breaks Down in Diverse Ways * 11 The Firefly Machine 12 Energy Metabolism in Cells * 13 The Malonic Acid Reagent ('Sodium Geometrate') * 14 Electrical Rhythmicity and Excitability in Cell Membranes * 15 The Aggregation of Slime Mold Amoebae * 16 Numerical Organizing Centers * 17 Electrical Singular Filaments in the Heart Wall * 18 Pattern Formation in the Fungi * 19 Circadian Rhythms in General * 20 The Circadian Clocks of Insect Eclosion * 21 The Flower of Kalanchoe * 22 The Cell Mitotic Cycle * 23 The Female Cycle * References * Index of Names * Index of Subjects

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/596B270197FE27DE5FABB598B6210622/S0025557200150892a.pdf/div-class-title-span-class-italic-the-geometry-of-biological-time-span-by-a-t-winfree-pp-544-dm68-corrected-second-printing-1990-isbn-3-540-52528-9-springer-div.pdf

The geometry of biological time , by A. T. Winfree. Pp 544. DM68. Corrected Second Printing 1990. ISBN 3-540-52528-9 (Springer)

Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.

http://science.sciencemag.org/content/sci/295/5557/1070.full.pdf

Phototransduction by retinal ganglion cells that set the circadian clock.

Molecular Bases for Circadian Clocks

▪ Abstract The peroxisome proliferator-activated receptors (PPARs) are a group of three nuclear receptor isoforms, PPARγ, PPARα, and PPARδ, encoded by different genes. PPARs are ligand-regulated transcription factors that control gene expression by binding to specific response elements (PPREs) within promoters. PPARs bind as heterodimers with a retinoid X receptor and, upon binding agonist, interact with cofactors such that the rate of transcription initiation is increased. The PPARs play a critical physiological role as lipid sensors and regulators of lipid metabolism. Fatty acids and eicosanoids have been identified as natural ligands for the PPARs. More potent synthetic PPAR ligands, including the fibrates and thiazolidinediones, have proven effective in the treatment of dyslipidemia and diabetes. Use of such ligands has allowed researchers to unveil many potential roles for the PPARs in pathological states including atherosclerosis, inflammation, cancer, infertility, and demyelination. Here, we presen...

The Mechanisms of Action of PPARs

Melatonin levels in the plasma of homing pigeons were measured by radioimmunoassay. In a 12∶12 LD cycle a robust daily rhythm of plasma melatonin was found in intact birds. This rhythm is significantly reduced in amplitude after pinealectomy, and disappears completely after the pinealectomized animals have been bilaterally enucleated. The results indicate that in the pigeon 70% of the nighttime peak of blood-borne melatonin comes from the pineal gland, while 17% comes from the retina. In addition, there is a relatively large amount (13%) of non-rhythmic melatonin of unidentified origin. The melatonin rhythm appears to be circadian in nature, since melatonin levels begin to fall before lights-on in LD, and rhythmicity persists in intact and pinealectomized birds for at least two cycles in DD. In conjunction with earlier studies, the present results are consistent with the hypothesis that melatonin serves as mediator of circadian information in the pigeon.

Contribution of pineal and retinae to the circadian rhythms of circulating melatonin in pigeons

The pineal gland, the retinas and perhaps other tissues as well may in some species produce melatonin that appears in significant quantities in the circulation. In at least one species, Japanese quail, the circadian rhythm in the levels of circulating melatonin reflects contributions from both the pineal and the retinas; in other species circulating melatonin may come exclusively from the pineal or perhaps only from the eyes. Comparative behavioural and physiological data from several bird and lizard species indicate that retinas and pineal glands fulfil similar endocrine roles. Current evidence suggests that in iguanid lizards either retinas or pineal glands, but not both in the same species, have important regulatory influences on circadian organization. This suggests that it should be relatively easy to influence the melatonin-forming ability of a tissue by natural selection, an interpretation bolstered by our finding that the ability to synthesize melatonin has been inadvertently eliminated in the pineal glands of laboratory mice, presumably by the selection involved in producing inbred strains. The genetics of melatonin synthesis in mice is briefly discussed.

Eyes--the second (and third) pineal glands?

Activity and reproductive state in the hamster: Independent control by social stimuli and a circadian pacemaker

The eyes and extraretinal brain photoreceptor(s) of the House Sparrow (Passer domesticus) both contribute to entrainment of the locomotor rhythm. During exposure to a light cycle of low intensity 25 sparrows were entrained and eight free-ran (Table 1). Birds free-running under these conditions became entrained after the intensity of light reaching the brain was increased by plucking their head feathers (Fig. 1). Following carbon black injection beneath the skin over the skull of 23 of these entrained birds, 13 remained entrained and 10 free-ran (Figs. 1 and 2). The injected-entrained birds resynchronized to a 6 hour phase delay in the light cycle. Six of these birds were blinded (bilateral orbital enucleation) and subsequently free-ran. When the carbon black was then removed they re-entrained (Fig. 3).

On the role of eyes and brain photoreceptors in the sparrow: Entrainment to light cycles

The inhibitory effects of melatonin on the testis of the golden hamster were investigated and the effect of melatonin on photostimulated testicular growth was determined. Hamsters were housed in a room provided with 14 hours of light and 10 hours of darkness to support optimal testicular function. Silastic capsules containing crystalline melatonin were implanted. In the 1st experiment the differences in average testicular weight of hamsters without implants was compared with those who received implants and maintained them for 60-80 days. In a 2nd study sexually mature hamsters were transferred from a light/dark of 14/10 hours to a photoperiod of 6/18 hours and received a melatonin-filled 25 or 200 mm Silastic capsule. An additional 5 groups of animals were transferred to a photostimulatory light/dark of 14/10 hours at the time they received either and empty Silastic capsule or a 25 50 100 or 200 mm melatonin-filled Silastic capsule. Melatonin administered in this manner prevented or suppressed light-induced testicular recrudescence in adult golden hamsters. Melatonin given at a dose of 150 mcg/day induced marked testicular regression in sexually mature hamsters maintained on photostimulatory long days.

Michael Menaker

Papers

Contribution of pineal and retinae to the circadian rhythms of circulating melatonin in pigeons

Eyes--the second (and third) pineal glands?

Activity and reproductive state in the hamster: Independent control by social stimuli and a circadian pacemaker

On the role of eyes and brain photoreceptors in the sparrow: Entrainment to light cycles

Melatonin-induced inhibition of testicular function in adult golden hamsters.