1. Circadian Rhythms: Lecture 4 Proseminar in Biological Psychology

2. Circadian Rhythms
Circa: "about” Dies: “day"
Circadian rhythms are physiological and behavioral characteristics that follow a daily, or circadian, pattern
24 hour period

3. Biological Rhythms Ultradian: cycles lasts shorter than a day
- milliseconds it takes for a neuron to fire
- 90 minutes sleep cycle (REM and NON REM sleep)
- hunger
- YOUR ATTENTION SPAN IN CLASS!
Infradian: cycles lasts longer than a day
- monthly menstrual cycle
- hibernation in animals
- bird migration
Circadian: cycles lasting 24 hr
- sleep-wake cycle
- body temperature
- testosterone levels: highest around 6:00 am, low at :00 pm

5. What dictates or governs our 24 hr cycle?

6. Environmental Cues: the light/dark cycle
Zeitgerbers: German for “Time Giver”
Meals
Temperature
Social activity
The tide (marine animals)
Entrainment

7. Zeitgebers
….no circadian rhythms?

8. We Do Not Need Environmental Cues for Circadian Rhythms
Persistence of rhythm in constant conditions
(LL/DD) & (Temp): tend to drift.. Under natural conditions, the clocks are precise.
Rhythm can be entrained
So  CR=daily rhythm is endogenously generated,
but still susceptible to modulation by 24-hour environmental cycles
endogenous "clock
How do we know that these
rhythms aren't entirely environmentally induced?

9. Jean Jacques d’Ortous de Mairan (1729)
First Time Evidence for a
Endogenous Clock
French Astronomer
Jean Jacques d’Ortous de Mairan (1729)
Heliotrope leaves closed at night
Observed the persistence of leaf movement in plants placed in constant dark
For 2 centuries nobody cared!!!

10. Psychiatrist August Forel (1910)
Noticed bees returning to
the breakfast table at the
same time of day to get jam

11. Psychiatrist August Forel (1910)
the bees returned at the same time of the day even when the food was not present
Hey Fred,
where’s the
jam?

12. von Frisch & Beling (1920)
First experiment done in the lab setting
Used Bees – set out sugar in water for several days
2. Bees came as expected
When not offered bees continued to show up
Performed the experiment in a salt mine = same result

13. Early Human Evidence of an Endogenous Clock
1931 – Wiley Post (Aviator)
Flew eastward around the world in
8 1/2 days (208 hrs)
- flying ability adversely affected
- sleep was disrupted
- general feeling of uneasiness
- nausea
First person to report JET LAG
internal clock not adjusted to environmental clock

14. Blind animals still show circadian rhythms
Other Evidence
Blind animals still show circadian rhythms
- Blind people show circadian cycles
- Some strains of Mice have virtually no retina
but still have circadian rhythms

15. Put Animals & Humans in “Constant Conditions”
Constant Conditions: LIGHT/LIGHT
DARK/DARK
“Free Running” = without cues
How close is the endogenous clock to 24 hr cycle?

16. TAU Depends on the Species Mus musculus (mouse) = 23.5
The ‘natural’ period of a biological rhythm
free-running in constant conditions:
TAU
Depends on the Species
Mus musculus (mouse) = 23.5
Homo Sapiens (Humans) = 25?24.18
Mesocricetus auratus (Hamster) = 24.1

17. the phase indicator while free
Measurement of Tau
Running Wheel Activity
14L/10D
Mouse (23.5) Hamster (24.1)
Onset of running
wheel activity is used
the phase indicator while free
Running = CT12
Actogram

18. Measurement of Tau in humans
Actiwatch

19. Suprachiasmatic Nucleus SCN Densely packed collection of small cells
The Clock – Oscillator
Suprachiasmatic Nucleus
SCN
Densely packed collection of small cells
(only 20,000) anterior hypothalamus
Midline in a shallow impression of the optic chiasm

20. Suprachiasmatic
Nucleus (SCN)
                                                       

21. SCN neurons project to other hypothalamic regions
Body Temp (Dorsal)
Sub paraventricular Zone
Sleep & waking (Ventral)
Sub paraventricular Zone
Feeding, sleep, temperature, hormones
SCN neurons project to other hypothalamic regions

22. SCN Retino-hypothalamic Tract
Retina-Geniculate-Striate Pathway – Ventral View
SCN
Retino-hypothalamic
Tract
Anterior Portion of the Hypothalamus  (SCN)
Superior to optic chiasm, receives input from optic nerves (RHT); this input synchronizes the “clock” in the SCN to the exterior day-night cycle

23. Innervation of the Pineal Gland in Humans –needs SCN
Dependent on the Light/Dark Cycle

24. Evidence for SCN - Biological Clock
1900’s Simpson & Galbriath
Rectal Temp every 2 hours for
2 months!!!!!

25. Evidence for SCN - Biological Clock
Lesions here interfere with circadian rhythms
1967 – C. P. Richter (rats)
Hypothalamic Lesions = disrupted eating
, drinking, activity
1972
Moore & Eichler
Stephan & Zucker
SCN
Lesions disrupted running wheel activity, drinking, hormones

26. Important! Changed the pattern of sleep not the amount
Evidence for SCN - Biological Clock
Lesions here interfere with circadian rhythms (rodents, primates)
Still show rhythms but desynchronized to environment L/D cycles (sleep at inappropriate times)
Abolishes rhythms completely
feeding, locomotor activity, sleep, temperature, hormones
Important! Changed the pattern of sleep not the amount

27. Increased metabolic activity (Schwartz & Gainer, 1977)
SCN
                                                       
night
day
Increased metabolic activity (Schwartz & Gainer, 1977)
So..SCN keeps track of day or night
But not whether you are diurnal or nocturnal
Injected 2-DG in rats…same results in squirrel monkeys

28. Other Major Evidence for SCN - Biological Clock
SCN cells invivo and invitro confer rhythminicity
- in tissue culture
- transplantation
Electrophysiological studies
- electrical activity continues even after surgical removal from hypothalamus
- other brain sites also show this but need a connection the SCN
Lesions of visual cortex have no effect on
rhythms
Severing RHT = free running rhythm

29. All show circadian rhythms Displaying individual rhythms
Tissue Culture
Electrophysiological studies - electrical activity continues even after surgical removal from hypothalamus
SCN neurons (4)
All show circadian rhythms
Displaying individual rhythms
…coolio

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

31. Ralph, M. R. and Menaker, M. (1989)
Transplantation Studies – Cooler Stuff
Ralph et al (1990)
Removed SCN from Mutant Hamsters (short tau 22 hrs)
Transplanted SCN into hamsters that had lesioned SCN
Restored….Sleep/Wake Cycle
….not regular cycle BUT….the short rhythms!!
VISA VERSA…same results!!!!  transplant to Mutants

32. Transplantation Studies – Coolest Stuff
Silver et al (1996)
Lesioned SCN of Hamster = abolished rhythms
Got donor SCN placed in tiny semipermeable capsule
transplanted into III ventricle
Chemicals, nutrients in NO SYNAPTIC TRANSMISSION
Reestablished rhythms!
??? Chemical

33. What makes the clock tick? Hands of the SCN
“Main Oscillator” (SCN cells)
But what about at the molecular level?
GENES
(contain the instructions that tells a cell
what its job will be)
Cells contain a newly discovered protein (clock protein)
that regulates gene function and which shows 24-hr
variations in cellular levels that appears to account for
24-hr variations in neuronal activity