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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

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

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


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

Environmental Cues: the light/dark cycle

  • Zeitgerbers: German for “Time Giver”

  • Meals

  • Temperature

  • Social activity

  • The tide (marine animals)



….no circadian rhythms?

  • 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?

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!!!

Psychiatrist August Forel


Noticed bees returning to

the breakfast table at the

same time of day to get jam

Psychiatrist August Forel


the bees returned at the same time of the day even when the food was not present

Hey Fred,

where’s the


  • 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

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

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

Put Animals & Humans in “Constant Conditions”

Constant Conditions: LIGHT/LIGHT


“Free Running” = without cues

How close is the endogenous clock to 24 hr cycle?

The ‘natural’ period of a biological rhythm

free-running in constant conditions:


Depends on the Species

Mus musculus (mouse) = 23.5

Homo Sapiens (Humans) = 25?24.18

Mesocricetus auratus (Hamster) = 24.1

Measurement of Tau

Running Wheel Activity


Mouse (23.5) Hamster (24.1)

Onset of running

wheel activity is used

the phase indicator while free

Running = CT12


The Clock – Oscillator

Suprachiasmatic Nucleus


Densely packed collection of small cells

(only 20,000) anterior hypothalamus

Midline in a shallow impression of the optic chiasm


Nucleus (SCN)

Body Temp (Dorsal)

Sub paraventricular Zone

Sleep & waking (Ventral)

Sub paraventricular Zone

  • Feeding, sleep, temperature, hormones

SCN neurons project to other hypothalamic regions

Retina-Geniculate-Striate Pathway – Ventral View




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

Evidence for SCN - Biological Clock

1900’s Simpson & Galbriath

Rectal Temp every 2 hours for

2 months!!!!!

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


Lesions disrupted running wheel activity, drinking, hormones

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




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

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

  • Tissue Culture

  • Electrophysiological studies - electrical activity continues even after surgical removal from hypothalamus

SCN neurons (4)

All show circadian rhythms

Displaying individual rhythms


Ralph, M. R. and Menaker, M. sustained circadian rhythm (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

Transplantation Studies – Coolest Stuff sustained circadian rhythm

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

What makes the clock tick? Hands of the SCN sustained circadian rhythm

“Main Oscillator” (SCN cells)

But what about at the molecular level?


(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