The sun; SOHO's EIT (Extreme-Ultraviolet Imaging Telescope)

1. The sun; SOHO's EIT (Extreme-Ultraviolet Imaging Telescope)

2. Earth-moon system from Galileo-1990 (from NASA photo gallery)

4. The astronomer Jean Jacques d’Ortous deMairan is usually credited with discovering “circadian rhythms” in heliotrope plants in 1729

5. Properties of Circadian Rhythms • Name is derived from “circa” (approximately) and “diem” (day) • When organisms are placed in constant conditions of DD or dim LL, they express a circadian rhythm with a period (t) of slightly less or slightly more than 24 hrs • These rhythms must be synchronized or “entrained” to local time so that the phase (f) of the internal rhythm corresponds to the f of the outside world.

6. Prokaryotes such as cyanobacteria (in this case Synechococcus sp.) express circadian rhythms in gene expression with a t of about 24 hrs (from Golden et al. 1999)

7. Fungi, such as the orange bread mold, Neurospora crassa, express a wide variety of circadian patterns. In this case, patterns of conidiation, or asexual spore formation, occur every 19-20 hrs. (from Bell-Pedersen, 1999)

8. Complex, multicellular animals express a wide variety of circadian rhythms. In this case, the activity/sleep and body temperature patterns of a single human subject is expressed in actogram format. The average t is 24.1-25 hrs (from Aschoff, 1981)

9. What are Biological Clocks? • Simply put, “biological clocks” are mechanisms by which organisms can tell time. The enable living things to predict internal and external events. • Internal oscillator • Zeitgeber or synchronizer • Output pathways • These clocks predict periods of varying magnitude • Annual (circannual) • Daily (circadian)

10. Circadian Clock Output Pathways Zeitgeber Outputs Input Pathway General Model of Circadian Clocks

12. The Hypothalamic Suprachiasmatic Nucleus (SCN) is the Master Pacemaker for Nocturnal Rodents and Probably Many, If Not All, Mammals (from Bittman, 1984)

13. SCN 2.2 Cells Induce Circadian Rhythms in NIH3T3 Cells (from Allen, Rappe, Cassone and Eannest, 2000)

14. SCN2.2 Cells Restore Circadian Rhythms NIH3T3 Cells Do Not SCNX SCNX NIH3T3 SCN2.2 (from Earnest, Liang, Ratliff and Cassone, 1999)

15. Recent advances in molecular genetics has identified specific genes that are important for circadian rhythms in many different types of organisms that are expressed rhythmically in clock-associated tissues. This is the expression pattern of mouse period genes in the SCN. (from Maywood et al. 2000)

16. “Common” Elements of Circadian Clocks Positive Elements Negative Elements Clock Genes Output (CCGs) Rhythmic Metabolism And Behavior Positive Elements in circadian loops: kaiA in Synechococcus wc1 and wc2 in Neurospora Clk, cyc, clock and bmal1 in animals Negative Elements in circadian loops: kaiC in Synechococcus frq in Neurospora Per, cry and tim in animals

21. In Mammals, At Least, Pineal Rhythmicity Derives Primarily From Rhythmic SCN Input via the Sympathetic Nervous System (from Bittman 1984)

22. Pinealectomy has no effect of rodent locomotor rhythms in DD (from Richter, 1967)

23. But Daily Administration Of the Pineal Hormone Melatonin Entrains Rat Circadian Rhythms. This Effect is Dose- and Phase-Dependent with an ED50 of 1-5 mg/kg (Cassone et al. 1986; Warren et al. 1993), Independent of the Pineal Gland (Warren et al. 1993) and Does Not Require Injections (ie. Infusions of Melatonin Work; Kirsch et al.1993) (from Redman, Ng, and Armstrong, 1983)

24. Circadian Rhythms in the Classroom • Visit Website for the NSF Center for Biological Timing to learn more about clocks • http://cbt4pc.bio.virginia.edu/tutorial • Also, there are specific classroom and home activities listed in that site at • http://cbt4pc.bio.virginia.edu/tutorial/CLASSACT.html

25. A copy of this presentation can be found at the following website http://www.bio.tamu.edu/facmenu/faculty/cassone.htm Visit the Biological Clocks Program At Texas A&M at http://www.bio.tamu.edu/clocks/