Overview
The brain, even in sleep, varies in its activity
Nocturnal; active during the night
Diurnal; active during the day
Melatonin always high at night; therefore, the light/melatonin signal
is therefore interpreted differently in diurnal and nocturnal animals.
Body temperature is low during sleep
Moving to the left; rhythm is shorter
Moving to the right; rhythm is longer
The circadian cycle
Circadian rhythm; internal process that regulates the sleep-wake
cycle and repeat ± every 24 hours.
Zeitgeber; external or environmental cue that entrains or
synchronizes an organism’s biological rhythms to the Earth’s 24-
hour light/dark cycle and 12-month cycle
There are also other biological rhtyms (annual, tidal (getij) etc.)
Time-isolation experiment;
For the first 7 days; person exposed to natural variation in ambient light and noises
that characterize day and night
For next 17 days; person cut off from all such cues (signalen). The sleep-wake cycle
increases
For several weeks; sleep-wake cycle increases even more.
(stay awak for 20h and sleep for 12)
Conclusions;
1. We have an internal clock (we maintain a rhythm in
the absence of external timing cues)
2. External sources (e.g. light) help to synchronize this
internal clock with the real world
Circadian rhythm development;
Babies are not born with 24-h clock mechanism in working order. It
takes ±4 months to develop circadian rhythm.
Other important internal stimulus that affects the sleep-wake cycle of
babies is hunger
, Receptors that sense light changes are in the retina.
The most important retinal detectors are not rod or cone cells
but neurons that lie within ganglion cell layer of retina (retinal
ganglion cell (RGC))
Rod and cone; are hyperpolarized when activated by
light
Retinal ganglion cells; are depolarized when activated
by light and they contain photopigment melanopsin.
RGC --> retinohypothalamic tract --> suprachiasmatic
nucleus (SCN) of the anterior hypothalamus -->
paraventricular nucleus of the hypothalamus --> spinal
cord --> preganglionic sympathetic neurons in the
intermediolateral zone of the lateral horns of thoracic
spinal cord --> superior cervical ganglion (SCG) -->
pineal gland near the dorsal thalamus.
The pineal gland synthesizes the sleep-promoting neurohormone melatonin
from tryptophan.
When melatonin is secreted into the bloodstream, melatonin modulates neural
activity by interacting with melatonin receptors on neurons in the SCN that in
turn influence the sleep-wake cycle
In elderly, pineal gland produces less melatonin.
The internal clock is the SCN (suprachiasmatic nucleus)
The neurons of the SCN itself contain melatonin receptors which inhibit SCN
activity as negative feedback signal during the darkness when melatonin is
released by the pineal gland.
So, when somebody is blind (missing rods and
comes) the circadian rhythm still works because
dependent on retinal ganglion cells.
The photosensitive retinal ganglion cells are a rare
(1-3%) subpopulation of ganglion cells whose
primary role is to signal light for unconscious visual
reflexes, such as pupillary constriction.
Molecular mechanisms of biological clocks
Key points in this complex regulatory scheme;
1. Concentrations of BMAL1 and the three PER
proteins cycle in counterphase
2. PER2 is a positive regulator of the BMAL1 loop
3. CRY is a negative regulator of the period and
cryptochrome loops