1. POSSIBLE FUNCTIONS of the CIRCADIAN CLOCK IS IT IMPORTANT AT ALL? YES! POSSIBLE FUNCTIONS DAILY PROGRAMING of PHYSIOLOGY PHOTOPERIODIC REPRODUCTION ANIMAL MIGRATION MCB 186 December 5, 2007

2. IS THE CIRCADIAN CLOCK IMPORTANT ? DOES THE CLOCK CONFER SELECTIVE ADVANTAGE? MAYBE NOT: NULL MUTANTS are VIABLE in ALL STUDIES TWO KINDS of STUDIES MEASURE LIFESPAN IN ANIMALS SUBJECTED TO NON-24 hr CYCLES RESONANCE EXPERIMENTS IN CYANOBACTERIA USING PERIOD MUTANTS

3. SURVIVIAL CURVES for FLIES in LIGHT/DARK CYCLES with PERIODS of 20, 24 AND 28 HOURS

4. FIVE HOUR LD PHASE SHIFTS EACH CYCLE

5. CYANOBACTERIA MUTANTS V.S. WILD TYPE IN DIFFERENT LD CYCLES C.H. Johnson lab

6. CYANOBACTERIA MUTANT Tau-28 V.S. WILD TYPE Tau-25 C.H.Johnson lab Two independent experiments

7. SOME FUNCTIONS OF THE CIRCADIAN CLOCK TIMED PHYSIOLOGY: SPECIFIC TIMES OF DAY/NIGHT Synthesis of specific proteins at specific times of day Insect eclosion acrophase is at time of daily temperature minimum. The internal bee clock; Visitations timed to time of flower openings Cyanobacteria, photosynthesis by day, nitrogen fixation by night. PHOTOPERIODIC REPRODUCTION: MEASURE DURATION OF DAY AND NIGHT -Plants: seasonal flowering, spring, summer or fall. -Animal seasonal reproduction; hamster only once per year. ANIMAL MIGRATION -Celestial navigation for migration (birds, butterflies, arthropods, fish, reptiles); knowledge of time of day required.

8. TIME of DAY PROGRAMS Different activities at different times of day involve different genes and proteins In circadian systems, different proteins are synthesized at different times of day Cyanobacteria carry out photosynthesis with oxygen production and nitrogen fixation at different times of day. Oxygen inhibits nitrogenase.

9. BEAN (top) and CANAVALIA CIRCADIAN LEAF MOVEMENTS

10. DROSOPHILA ENTRAINMENT TO FULL LD CYCLES PITTENDRIGH ACROPHASE DEPENDS ON PHOTO-FRACTION

11. TEMPORAL SEPARATION OF CELL BIOCHEMICAL ACTIVITIES IN CYANOBACTERIA ( OXYGEN, NITROGENASE ETC) MITSUI ET AL 1986

12. PATTERNS of CLOCK-CONTROLLED PROTEIN SYNTHESIS in Gony Markovic et al., 1996 J. Biol. Rhythms 11 p21 unknown p32 PCP p33 OEE1 p45 GAPDH p55 Rubisco II p75 Luciferin binding protein

13. PHOTOPERIODISM DISCOVERY: Garner & Allard, 1920 TOBACCO FLOWERING ONLY IN FALL WITH SHORT DAYS OTHER PLANTS SHOWN TO FLOWER WITH LONG DAYS. STILL OTHERS DAY LENGTH NEUTRAL TERMINOLOGY CORRECTED: Hamner & Bonner, 1938 LENGTH OF THE NIGHT, NOT THE DAY, IS CRITICAL LIGHT INTERRUPTIONS OF NIGHT BLOCK RESPONSE, DARK INTERRUPTIONS OF DAY DO NOT BLOCK INCORRECT TERMINOLOGY STILL IN USE:

14. DAY LENGTH AT DIFFERENT LATITUDES & SEASONS

15. HAMSTER TESTIS WEIGHT IN DIFFERENT FULL PHOTOPERIODS Elliott, 1976

16. PHOTOPERIODIC INDUCTION OF CYSTS IN GONYAULAX

17. SOY BEAN (SHORT DAY PLANT) 0.5 hr LIGHT INTERRUPTION of LONG DARK PERIOD WARING, 1954

18. H. NIGER (LONG-DAY PLANT) 2 hr LIGHT INTERRUPTION OF LONG DARK PERIOD

19. SOYBEAN (short day) FLOWERING IN DIFFERENT LD CYCLES

20. MODELS FOR PHOTOPERIODISM HOUR GLASS: Substance X builds up during dark Explains night interruption by brief light exposure Does not explain oscillation of long dark periods. ENDOGENOUS OSCILLATION Explains circadian recurrence of susceptibility to brief light exposure during prolonged DD External Coincidence model: Night interruption causes delays & advances

21. EXTERNAL COINCIDENCE: POSTULATED PHOTOPERIODIC EFFECTS ON AN ORGANISM WITH A CIRCADIAN tau OF 24.5 hr

22. ENTRAINED T of HAMSTER ACTIVITY RHYTHM DEPENDS on PERIOD of SINGLE PULSE T CYCLE and PULSE is POSITIONED DIFFERENTLY Elliott 1976 Tau for hamster is very close to 24 h Both T cycles cause phase shifts, + & - ADVANCES DELAYS

23. HAMSTER TESTICULAR RESPONSES to T CYCLE PERIOD LENGTH

24. DROSOPHILA ENTRAINMENT TO FULL LD CYCLES PITTENDRIGH

25. PHASE ANGLES WITH DIFFERENT TWO PULSE SKELETONS Pittendrigh

26. BISTABILITY IN HAMSTER ENTRAINMENT SKELETON PHOTOPERIOD 13.5:0.25:10:0.25 hrs ANIMAL C15 ACTIVE in SHORT NIGHT TESTES MAINTAINED; ANIMAL C16 ACTIVE in LONG NIGHT; TESTES REGRESSED

27. SKELETON PHOTOPERIOD PHASING GIVES DIFFERENT RESPONSES

28. ARE HUMANS AFFECTED by PHOTOPERIOD? It appears so! ANNUAL CYCLES DAILY ENTRAINMENT PHASE

29. 1824 1947

30. HUMAN ANNUAL CONCEPTION RHYTHMS

31. SOCIAL INFLUENCES on the ANNUAL CONCEPTION RHYTHM

33. Effect of Residence Locations on Sleep Acrophase (n=21,600) Germany Roenneberg, 2006

34. DEPENDENCE of TIME of MID-SLEEP on LONGITUDE 8.5 O =34min and RELATION to POPULATION DENSITY Rural and towns less than 300,000 persons 300,000 - 500,000 > 500,000 Roenneberg, 2006

35. DAYLIGHT SAVING TIME RELATED to SLEEP PHASE and DURATION

36. CIRCANNUAL RHYTHMS IN SQUIRRELS & GONYAULAX

37. FUNCTIONS of the CIRCADIAN CLOCK CELESTIAL NAVIGATION -Animal migration (birds, butterflies, arthropods, fish, reptiles); knowledge of time of day required.

41. DIRECTION OF STARLING MIGRATORY ACTIVITY Kramer,1950 a) clear sky b)overcast c),d) direction of incident light deflected by mirrors

42. DIRECTION OF DEPARTURE IN PIGEONS ALTERED AFTER EXPOSURE TO LD CYCLE ALTERED BY 6 hr Schmidt-Koenig,1961

43. SHIFTING THE DIRECTIONAL RESPONSE OF PIGEONS

45. DELAYED SLEEP PHASE INSOMMNIA THERAPY Deficiency in advance phase shifts Treatment: Impose repeated delays until patient is back in phase.