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Biological clocks

Biological clocks. Clock periods Circannual Circalunidian Circadian Clock mechanisms Entrainment Neural location Genetic basis. Hibernation follows annual rhythm in golden-mantled ground squirrels. Five animals were isolated at birth and kept in darkness at 3 o C.

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Biological clocks

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  1. Biological clocks • Clock periods • Circannual • Circalunidian • Circadian • Clock mechanisms • Entrainment • Neural location • Genetic basis

  2. Hibernation follows annual rhythm ingolden-mantled ground squirrels Five animals were isolated at birth and kept in darkness at 3oC

  3. Testes growth and feather molt in stonechats follows annual cycles Nestlings were removed from Kenya and reared in Germany with constant temperature and photoperiod and yet retain annual molt and testes cycles. Notice that the clock period drifted.

  4. Horseshoe crabs mate on full moonwhy?

  5. Neap tide Sun and moon are perpendicular, tidal excursion is least Spring tide Sun and moon align, tidal excursion is greatest Lunar position affects the tides

  6. Neotropical bats exhibit lunar phobia

  7. Kangaroo rat feeding shows lunar cycles K-rat activity at a feeder is confined to dark periods occurred during period of seed shortages

  8. Isopod activity follows daily tidal flow Isopods are usually covered with water at high tide. They retain this activity even when kept in the lab with no tidal fluctuation.

  9. Entrainment by environmental cycles • Temperature compensation • Clock cycles do not change with temperature • Environmental cues set cycle period • Species specific • Types of cues (zeitgebers) • Photoperiod • Light pulse • Food availability

  10. Cricket calling entrains to dark Constant light for 12 days 12 h light/dark for 12 days

  11. Mouse activity entrains to light 12h light:12h dark 24 h dark 10 min light 10 mins of light per day are sufficient to reset the clock

  12. Mole-rats lack daily cycles

  13. Clock mechanisms • Location of the clock • Suprachiasmatic nucleus of the hypothalamus • Pineal gland • Clock genes • Period • Timeless • Tau (doubletime)

  14. Mammal and bird clocks reside in the suprachiasmatic nuclei (SCN), which is in the hypothalamus

  15. Period In hamsters, SCN lesion disrupts clock while SCN transplant restores clock

  16. Isolated rat SCN cells exhibit clock activity Isolated caudate (upper brainstem) cells do not cycle, but isolated SCN cells do cycle

  17. Isolated neurons from rat SCN exhibit circadian rhythym Neural firing is stopped with application of tetrodotoxin (TTX), which blocks sodium channels, but clock kept ticking!

  18. Pineal glands respond to light cycles Melatonin release from chicken pineal glands cultured in vitro Light cycles No light cycles

  19. Distribution of circadian clocks in tissues and taxa

  20. Mammalian clock pathways

  21. period alleles exhibit altered circadian rhythyms in Drosophila melanogaster

  22. Genetic basis of the clock in flies http://www.nimh.nih.gov/publicat/bioclock.cfm • NOON: per and tim genes are turned on by CLOCK-CYCLE complex, which binds to promoter • SUNSET: PER and TIM transcription occurs • NIGHT: PER and TIM proteins build up inside the cell, and as a complex can enter nucleus • dbt codes for an enzyme that adds a phosphate to PER, which causes it to be destroyed & adds time delay • DAWN: Cryptochromes absorb blue light and activate cry gene expression. TIM protein is degraded by CRY protein. • PER is released from PER-TIM complex and broken down, so CLOCK-CYCLE can activate per and tim

  23. Genetic basis of the clock in mammals • per codes for a protein (PER) that gradually builds up over time • tau codes for an enzyme that breaks down PER • tim codes for a protein (TIM) that binds with PER to cross the membrane and suppress transcription of PER • Photoreceptor not yet known • Cycle repeats every 24 h

  24. Clock summary • per/tim/tau(dbt) genes control pacemaker • Pacemaker occurs in SCN in vertebrates, but is distributed in brain cells in some insects • SCN signals pineal to release melatonin. Melatonin causes entrainment • Short pulses of light entrain SCN and pineal cells • Photoreceptors occur in the pineal and eyes of birds • Photoreceptors occur in retina of mammals • Drosophila, honey bees, hamsters and humans share same genes - likely common ancestor was a flatworm that lived about 600 MYA

  25. Clock neurons in fly brains http://www.bio.brandeis.edu/faculty/hall.html Hall, J.C. 2003. Genetics and molecular biology of rhythms in Drosophila and other insects. Adv. Genet. 48: 1-286

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