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Circadian Rhythms: Lecture 4 Proseminar in Biological Psychology

Circadian Rhythms: Lecture 4 Proseminar in Biological Psychology. Circadian Rhythms. Circa: "about” Dies: “day" Circadian rhythms are physiological and behavioral characteristics that follow a daily, or circadian, pattern. 24 hour period. Biological Rhythms.

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Circadian Rhythms: Lecture 4 Proseminar in Biological Psychology

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  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 6:00 pm

  4. What dictates or governs our 24 hr cycle?

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

  6. Zeitgebers ….no circadian rhythms?

  7. 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?

  8. 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!!!

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

  10. 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?

  11. 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

  12. 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

  13. 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

  14. 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?

  15. 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

  16. 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

  17. Measurement of Tau in humans Actiwatch

  18. 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

  19. Suprachiasmatic Nucleus (SCN)

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

  21. 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

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

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

  24. 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

  25. 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

  26. 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

  27. 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

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

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

  30. 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

  31. 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

  32. 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

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