1. CLOCKS

2. Clocks: What is a clock? How does a biological clock compare with a mechanical clock? Why have a circadian clock? What are the properties of circadian clocks? How do we set the circadian clock?

3. CLOCKS Measure Time

4. All clocks must have two basic components: 1.a regular, constant or repetitive process or action or OSCILLATION to mark off equal increments of time 2.a means of keeping track of the increments of time and displaying the result.

5. Oscillations are turned into time by matching them to solar (light/dark) cycle

6. Text 0 90 180 270 360 External Clock time (Time of Day) Internal clock time Earths rotation 6 a.m.

7. Mechanical Clock Oscillator: a regular, constant or repetitive process or action to mark off equal increments of time. Pendulum Balance wheels Vibrating crystal - quartz electromagnetic waves – atomic clocks Output: a means of keeping track of the increments of time and displaying the result. position of clock hands digital time displays.

8. MECHANICAL CLOCKS Pendulum clock 1656 Christiaan Huygens 1721 George Graham 1889 Siegmund Riefler Balance Wheels 1876 Quartz clocks 1920’s 1969 Seiko 1972 Pulsar 1980 Swatch Atomic clocks 1955 cesium

9. Mechanical Clock Oscillator: a regular, constant or repetitive process or action to mark off equal increments of time. Pendulum Balance wheels Vibrating crystal - quartz electromagnetic waves – atomic clocks Output: a means of keeping track of the increments of time and displaying the result. position of clock hands digital time displays. Resetting Mechanism manual Biological Clock Oscillator: pacemaker neurons Output: overt biological rhythms Resetting Mechanism - zeitgeber Anticipation

10. Properties of Biological Clocks  They continue to run under constant conditions. tau = not exactly 24h  They are Temperature Compensated  They are affected by Light Intensity.  They are under Genetic Control.  They are Adjustable Zeitgeber Range of Entrainment

11. Why have a circadian clock? Coordinates body activities with each other Synchronizes individual’s activity with the environment Anticipates predictable rhythmic changes in our environment Gives animal best chance for survival

12. Where is the circadian clock? hypothalamus scn

14. Optic Nerve Optic Chiasm

15. Suprachiasmatic Nucleus (SCN) Neuropeptides VIP (vasoactive intestinal polypeptide GRP (Gastrin releasing peptide) PHI (peptide histidine isoleucine) Dorsomedial division Ventrolateral Division

16. Curtis Richter Lesion Stephan and Zucker Ablation Arrhythmic

17.  Ablation eliminates circadian rhythms

18. Criteria for identification of the clock:  Ablation eliminates circadian rhythms  Electrolytic Lesion  Chemical Lesion  Circadian rhythm of activity exists within the clock  Electrophysiological  Metabolic -2Deoxyglucose  Neurochemical synthesis  Isolation of clock from rest of brain in vivo eliminates overt rhythms but does not eliminate rhythm within the clock.  Remove clock from the animal and clock still exhibits a sustained circadian rhythm  Transplant clock cells back into lesioned, arrhythmic animal restores rhythms

19. Stereotaxic instrument

20. Rhythmic Activity in situ Inouye and Kawamura – 1970s – Electrical Activity Schwartz et al – 1980 – Metabolic Activity

21. Remove clock from the animal and clock still exhibits a sustained circadian rhythm

25. Rhythms within SCN Electrical activity – high during day, low at night Metabolic activity – active during day; inactive at night Neurotransmitter synthesis

27. Oscillator Lesion Arrhythmia Ablation Humoral SCNx temporal A structure exhibiting a regular variation Injury Without a rhythm Total removal Transported in the blood SCN lesioned Related to time

28. Tau mutant A circadian period different from 24h Wild type Non-mutant, control organism Homozygous 2 identical alleles for a trait Heterozygous 2 different alleles for a trait In vitro in an artificial environment outside the living organism In vivo In the living organism Electrode An instrument which conducts an electric current Explant tissue removed from its normal place of growth and placed into tissue culture Organotypic Electrolyic made with an electricl current Torpor dormant or lethargic state

29. Peripheral Oscillators  Retina  Fibroblasts  Liver