Transcript Biological Rhythms I

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
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
A Hamster for All Seasons
seasonal changes in coat color of Siberian hamsters
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, waketime in research on circadian rhythms and other aspects of chronobiology.
How Activity Rhythms where Measured a long time ago
Lights on later
free-running
The Effects of Lesions in the SCN
Lesion -
Brain Transplants Prove That the SCN Contains a Clock
Fetal SCN cells with tau mutation
The Retinohypothalamic Pathway in Mammals
Components of a Circadian System
Note: the eye part of this image is anatomically wrong
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.
An Unobstructed View
A Molecular Clock in Flies and Mice
input from retina
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
Per1brdm1
1-h shorter pd
Per1ldc
0.5-h shorter pd/arrhythmic
Per1−/−
0.5-h shorter pd
Per2brdm1
1.5-h shorter pd/arrhythmic
Per2ldc
Arrhythmic
Per1
Per2
4–8
6–12
10–16
14–18
Per3
4–9
10–14
Per3−/−
0–0.5-h shorter pd
Cry1
8–14
14–18
Cry1−/−a
1-h shorter pd
Cry2
8–14
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
0.5-h shorter pd/disrupted photic entrainment
Rorβ
4–8
18–22
Rorβ−/−
0.5-h longer pd
Rorγ
N/Ac
16–20/variousb
Rorγ−/−
Unknown
NPAS2
N/Ac
NPAS2−/−
0.2-h shorter pd
CK1ε (Csnk1ε)
Constitutive
Constitutive
CK1εtaud
4-h shorter pd
CK1δ (Csnk1δ)
Constitutive
Constitutive
Csnk1δ−/+
0.5-h shorter pd
0–4
When the Endogenous Clock Goes Kaput
Mouse with clock/clock mutation
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
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
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
Regulation of the Pineal Gland
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
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.
Electrophysiological Correlates of Sleep and Waking
A Typical Night of Sleep in a Young Adult
Typical: a regular sleep wake pattern with ~ 8 hours of sleep
Oh, How I Hate to Get Up in the Morning
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