Circadian Rhythms and the Biological Clock:An Historical Introduction

Outline

• What are Circadian Rhythms?

• Why do we call the mechanism that regulates circadian rhythms a “Biological Clock”?

What are the Important Characteristics of a “Clock”?

1. It can be set to local time2. It can tell you the time of day.3. It can be used to measure lapse of time

A Human Sleep Wake Cycle in the Laboratory

24-h Day

25-h Day

24-h Day

Unscheduled Day

Charles Czeisler

Human Isolation Chamber in Sapporo Japan

Jurgen Aschoff

Circadian (Circa, Dies) Rhythms are Ubiquitous in Living Systems and Have Similar Properties

Circadian Rhythms: The Basic Model

+ =

EntrainedRhythm

FreerunningRhythm

Light Cycle

Origins of the Field of “Chronobiology”: Early Observations of Daily Rhythms in Plants

Scarlet Pimpernel

Day

Night

The first written record: In the 4th century BC Adrosthenes, a scribe for Alexander the Great, wrote that he observed on the march to India that the leave of the tamarind tree always opened during the day and closed at night.

Jean-Jacques deMairan’s

Experiment (1729)“The progress of true science,

which is the experimental kind, is necessarily slow”

The first hint that daily rhythms are internally driven

Daily rhythms of "sleep movements" of leaves (Mimosa).

The Next 200 Years

•1832 de Candolle discovers that the Mimosa opens it’s leaves 1-2 hours earlier each day

•1906 Simpson and Gailbraith find daily temperature rhythms in monkeys persist in constant darkness

•1922 Richter shows persistent rhythms of activity in animals (rats)

The Birds

And the Bees

Recognizing Local Time of Day

Karl von Frisch

Daily Rhythms in Nectar Secretion

Daily rhythm of nectar secretion in Hoya carnosa. Matile, P, (2005) Bee visits to a crookneck squash

patch (peak nectar production at 9:00 AM) Edge et al. (2012)

Porcelainflower

No News to the Poets!

Andrew Marvell (1621-1678)from Thoughts in a Garden

“And as it works, the industrious beecomputes its time as well as we.How could such sweet and wholesome hoursbe reckoned but with herbs and flowers”

Dance Language of the Bees: Measuring Lapse of Time

The Waggle Dance

Time -Compensate

dSun Compass

Orientation

When a bee finds a food source some distance from the hive, he can return to the hive and, through dance, can communicate the direction (with respect to the sun) and the distance of the food source. The movement of the sun across the sky is compensated for by the bee’s internal, biological clock.

The Round Dance

A vertical waggle indicates directly towards the sun

Sun Orientation in Starlings

Gustave Kramer 1950Klaus Hoffman 1960

Circadian Clocks and Sun-Compass Orientation

“Photoperiodism” and Measuring Daylength

Summer (Long Day)Fall (Short Day)

Garner & Allard, 1920

Michael Menaker

Photoperiodic Time Measurement in a Hamster

• Released from the pineal gland at night. In mammals, synthesis and release are controlled by the Biological Clock.

• In many mammals it is involved in regulating seasonal cycles that are controlled by the length of the daily photoperiod (reproduction, coat color, fat accumulation, hibernation, etc.)

Siberian Hamsters from long days/short nights (summer) and short days/long nights (winter). Testes from Long-day and Short-day

hamsters

• In humans melatonin’s function is not yet fully understood, though in the popular press it has been touted as a cure for everything from insomnia to Alzheimer’s disease.

Pineal Gland & Melatonin

The Problem of Temperature

Early Studies of Human Circadian Rhythms

http://www.bgamplifier.com/lifestyle/newsreel-sleep-experiment-in-mammoth-cave/youtube_dc3b38ce-f3a9-11e2-b516-0019bb2963f4.html

Siffre’s Cave Experiment in Texas, 1972. He emerged after 179 days, but he thought he had been in the cave for only 151 days