1. Biorhythm From Wikipedia, the free encyclopedia
Biorhythm (from Greek βίος - bios, "life"[1] and ῥυθμός - rhuthmos, " any regular recurring motion, rhythm"[2]) is an attempt to predict various aspects of a person's life through simple mathematical cycles. Most scientists believe that the idea has no more predictive power than raw chance,[3] and consider the concept an example of pseudoscience.
Ry Cooder Get Rhythm

2. Biological Rhythms
Chronobiology is a field of biology that examines periodic cycles known as biological rhythms in living organisms as an adaptation to solar- and lunar-related rhythms.
Circadian rhythm: “about one day” is a 24-hour cycle
sleep-wake cycle
body temperature
melatonin
Ultradian rhythm: more then once a day
3 hour cycle of growth hormone production
appetite
sleep stages; for example REM
Infradian rhythms: less then once a day
menstrual cycle
reproductive cycles; i.e. breeding seasons
annual migrations

3. A Hamster for All Seasons seasonal changes in coat color of Siberian hamsters
Some biological rhythms are shorter, such as bouts of activity, feeding, and hormone release.
These ultradian rhythms occur more than once per day.
Period length can be from minutes to hours.
Other biological rhythms are long, such as body weight and reproductive cycles.
An endogenous circannual clock, separate from the SCN, runs at approximately 365 days.
Infradian rhythms occur less than once per day.

4. How Activity Rhythms Where Measured A Long Time Ago
are measured today
voluntary wheel running is one of the most widely used indicators of activity, wake-time in research on circadian rhythms and other aspects of chronobiology.

5. How Activity Rhythms where Measured a long time ago
Lights on later
Circadian rhythms are generated by an endogenous (internal) clock.
A free-running animal is maintaining its own cycle with no external cues, such as light.
The period, or time between successive cycles, may not be exactly 24 hours.
A phase shift is the shift in activity in response to a synchronizing stimulus, such as light or food.
Entrainment is the process of shifting the rhythm.
The cue that an animal uses to synchronize with the environment is called a zeitgeber–“time-giver”.
free-running

6. The Effects of Lesions in the SCN
The biological clock is in the suprachiasmatic nucleus (SCN)–located above the optic chiasm in the hypothalamus.
Studies showed that circadian rhythms were disrupted in SCN-lesioned animals.
Isolated SCNs can maintain electrical activity synchronized to the previous light cycle

7. Brain Transplants Prove That the SCN Contains a Clock
Fetal SCN cells with tau mutation

8. The Retinohypothalamic Pathway in Mammals
Circadian rhythms entrain to light–dark cycles using different pathways, some outside of the eye.
In amphibians and birds, the pineal gland is sensitive to light.
In mammals, light information goes from the eye to the SCN via the retinohypothalamic pathway.
The retinohypothalamic pathway consists of retinal ganglion cells that project to the SCN.
These ganglion cells do not rely on rods and cones.
Most of these retinal ganglion cells contain melanopsin, a special photopigment, that makes them sensitive to light.

9. Components of a Circadian System
Note: the eye part of this image is anatomically wrong
The retinohypothalamic pathway consists of retinal ganglion cells that project to the SCN.
These ganglion cells do not rely on rods and cones.
Most of these retinal ganglion cells contain melanopsin, a special photopigment, that makes them sensitive to light, especially blue light.
Intrinsically photosensitive Retinal Ganglion Cells (ipRGCs), also called photosensitive Retinal Ganglion Cells (pRGC), or melanopsin-containing retinal ganglion cells, have slow response and signal the presence of light over the long term.

10. An Unobstructed View Rods are absent from the fovea.
They are more numerous in the periphery and are more sensitive to dim light than cones are.
Rod input converges on ganglion cells in the scotopic system.

11. A Molecular Clock in Flies and Mice
input from retina
Molecular studies in Drosophila using mutations of the period gene helped to understand the circadian clock in mammals.
SCN cells in mammals make two proteins: Clock, Cycle
Clock and Cycle proteins bind together to form a dimer.
The Clock/Cycle dimer promotes transcription of two genes: Period (per), Cryptochrome (cry)
Proteins arising from per and cry bind to each other and to a third one,Tau.
The Per/Cry/Tau protein complex enters the nucleus and inhibits the transcription of per and cry.
No new proteins are made, until the first set degrades and the cycle begins again every approximately 24 hours.
Light entrains the molecular clock in different ways.
In flies, light reaches the brain directly and degrades a clock protein.
In mammals, retinal ganglion cells detect light and release glutamate in the SCN.
Glutamate triggers events that promote production of the Per protein, which in turn shifts the clock and the animal’s behavior.

12. Molecular components of the mammalian circadian clock
Caroline H. Ko and Joseph S. Takahashi
Hum. Mol. Genet. (2006) 15 (suppl 2): R271-R277.
Gene
Average circadian time at peak transcript level
Allele
Mutant phenotype
SCN
Periphery
Bmal1 (Arntl)
15–21
22–02
Bmal1−/−
Arrhythmic
Clock
Constitutive
21–03
ClockΔ19/Δ19
4-h longer pd/arrhythmic
Clock−/−
0.5-h shorter pd
Per1
4–8
10–16
Per1brdm1
1-h shorter pd
Per1ldc
0.5-h shorter pd/arrhythmic
Per1−/−
Per2
6–12
14–18
Per2brdm1
1.5-h shorter pd/arrhythmic
Per2ldc
Per3
4–9
10–14
Per3−/−
0–0.5-h shorter pd
Cry1
8–14
Cry1−/−a
Cry2
 8–12
Cry2−/−a
1-h longer pd
Rev-erbα (Nr1d1)
2–6
 4–10
Rev-erbα−/−
0.5-h shorter pd/disrupted photic entrainment
Rorα
6–10
Arrhythmic/variousb
staggerer
Rorβ
18–22
Rorβ−/−
0.5-h longer pd
Rorγ
N/Ac
16–20/variousb
Rorγ−/−
Unknown
NPAS2
 0–4
NPAS2−/−
0.2-h shorter pd
CK1ε (Csnk1ε)
CK1εtaud
4-h shorter pd
CK1δ (Csnk1δ)
Csnk1δ−/+

13. When the Endogenous Clock Goes Kaput
Mouse with clock/clock mutation
Gene mutations show how important the clock is to behavior in constant conditions:
In tau mutations the period is shorter than normal.
Double Clock mutants–severely arrhythmic

14. SCN Output Regulates Many Functions
SCN sends information to other hypothalamic areas
Pre-optic Area (POA)
Para Ventricular Nucleus (PVN)
Dorsal Medial Hypothalamus (DMH)
Organizes the time course of metabolic events
Physiological
body temperature
blood pressure
metabolism
Hormonal: see next slide
Behavioral processes
sleep/wake cycle
rest/activity cycle
reproductive
eating

15. SCN Regulates Hormones
Thyroid via POA - TRH – TSH
Adrenal Corticosterone
DMH - CRH – ACTH pathway
PVN – sympathetic pathway to adrenal cortex
Melatonin via PVN - sympathetic pathway to pineal gland
Sex steroids via POA - GnRH – LH or FSH
Leptin via PVN – autonomic innervation of adipose tissue
Insulin via PVN – autonomic innervation of pancreas

16. Pineal Gland produces Melatonin
Light Signal Circuit
special cells in retina detect light
signals and entrains the suprachiasmatic nucleus (SCN)
Axons from the SCN to the paraventricular nuclei (PVN)
PVN to the spinal cord superior cervical ganglia (SCG)
SCG connects into the pineal gland
Production of melatonin
stimulated by darkness
inhibited by light
Melatonin (5-methoxy-N-acetyltryptamine)
hormone found in all living creatures from algae to humans
levels vary in a diurnal cycle

17. Regulation of the Pineal Gland
BP6e-Fig jpg The pineal gland is a single gland on top of the brainstem.
It secretes an amine hormone, melatonin, almost exclusively at night.
Melatonin provides a signal that tracks day length and the seasons.
Melatonin (5-methoxy-N-acetyltryptamine)
hormone found in all living creatures from algae to humans
levels vary in a diurnal cycle
Production of melatonin
stimulated by darkness
inhibited by light
Light Signal Circuit
special cells in retina detect light
signals and entrains the suprachiasmatic nucleus (SCN)
Axons from the SCN to the paraventricular nuclei (PVN)
PVN to the spinal cord superior cervical ganglia (SCG)
SCG connects into the pineal gland

18. Functions of Melatonin
Timing of hibernation, changes in metabolism
Timing of (seasonal) breeding
Timing of sexual maturity
Timing of sleep
promotes drowsiness
increase REM sleep time and vividness of dreams
counteract immunodeficiences
cell-protective “antiapoptotic” for immune cells
a powerful antioxidant to reduce free radicals

19. Cell-autonomous Circadian Oscillator
Most peripheral organs and tissues such as liver, pancreas, skeletal muscle, intestine, and adipose tissue can express circadian oscillations in isolation
Most common is Per gene for Per protein
Receive, and may require, input from the SCN in vivo
Can generate behavioral rhythms in vivo in the absence of the SCN
Control rhythms of gene transcription for metabolic pathways, glucose homeostasis and lipogenesis
Interact with each other and with the system as a whole.

20. Electrophysiological Correlates of Sleep and Waking
Electrical brain potentials can be used to classify levels of arousal and states of sleep.
Electroencephalography (EEG) records electrical activity in the brain.
Electro-oculography (EOG) records eye movements.
Electromyography (EMG) records muscle activity.
Two distinct classes of sleep:
Slow-wave sleep (SWS) can be divided into four stages and is characterized by slow-wave EEG activity.
Rapid-eye-movement sleep (REM) is characterized by small amplitude, fast-EEG waves, no postural tension, and rapid eye movements.
The pattern of activity in an awake person contains many frequencies:
Dominated by waves of fast frequency and low amplitude (15 to 20 Hz)
Known as beta activity or desynchronized EEG
Alpha rhythm occurs in relaxation, a regular oscillation of 8 to 12 Hz.
Four stages of slow-wave sleep:
Stage 1 sleep shows events of irregular frequency and smaller amplitude, as well as vertex spikes, or sharp waves.
Heart rate slows, muscle tension reduces, eyes move about
Lasts several minutes
Stage 2 sleep:
Defined by waves of 12 to 14 Hz that occur in bursts, called sleep spindles
K-complexes appear–sharp negative EEG potentials
Stage 3 sleep:
Continued sleep spindles as in stage 2
Defined by the appearance of large-amplitude, very slow waves called delta waves
Delta waves occur about once per second.
Stage 4 sleep:
Delta waves are present about half the time.
REM sleep follows:
Active EEG with small-amplitude, high-frequency waves, like an awake person
Muscles are relaxed–called paradoxical sleep

21. A Typical Night of Sleep in a Young Adult
Typical: a regular sleep wake pattern with ~ 8 hours of sleep
In a typical night of young adult sleep:
Sleep time ranges from 7–8 hours
45–50% is stage 2 sleep, 20% is REM sleep
Cycles last 90–110 minutes, but cycles early in the night have more stage 3 SWS, and later cycles have more REM sleep.

22. Oh, How I Hate to Get Up in the Morning
At puberty, most people shift their circadian rhythm of sleep so that they get up later in the day.
However, most high schools require adolescents to arrive even earlier.
Later starts improved attendance and enrollment, and reduced depression and in-class sleeping.

23. Historical Changes in Sleep Patterns
“Sleep We Have Lost: Pre-industrial Slumber in the British Isles”
by A. Roger Ekirch (2001)
"first sleep" and “second sleep”
Interrupted by up to an hour or more of quiet wakefulness midway through the night
Sleep's principal contribution was not merely physiological but psychological
Natural Sleep and Its Seasonal Variations in Three Pre-industrial Societies
Yetish et al., 2015, Current Biology 25, 1–7, November 2, 2015
The Hadza in northern Tanzania, the Kalahari San, the Tsimane in Bolivia
Sleep periods, the times from onset to offset, averaged 6.9–8.5 hour, with sleep durations of 5.7–7.1 hour,
Sleep duration was strongly linked to time of sleep onset, on average, 3.3 hr after sunset
Sleep offset “Awakening” was very regular and usually before sunrise
During summer one hour less sleep then during winter sleep
Sleep period was not interrupted by extended periods of waking
Sleep terminated with vasoconstriction near the nadir of daily ambient temperature