Week 12 - circadian rhythms Flashcards
what species have circadian rhythms?
bacteria, protozoa, plants funghi and animals
what do humans have circadian rhythms for?
behaviour, alertness, mood, body temperature and hormone levels.
are circadian rhythms only based on changes in the environment?
no, the circadian rhythm is endogenous. almost every cell in the body has its own internal clock that can be entrained by sensory signals which act through a master clock in the brain.
gene involved in circadian rhythms
A gene called Period, or per, on the X chromosome shows a 24 hour cycle, it is transcribed mostly early in the night, so its mRNA is most abundant around 10pm. its protein product PER, is most abundant 6 hours later.
when are per and PER most abundant
the gene per, its mRNA is most abundant at 10pm, the protein PER is most abundant 6 hours later.
transcription translation feedback loop of PER and per
PER represses transcription of per (in the absense of PER, mRNA levels do not cycle), i.e. PERA and its mRNA drive each other’s cycling in a TTFL
timeless (tim) gene
tim mRNA and its protein product, TIM, also oscillate like per mRNA and PER
TIM and PER interactions
TIM binds PER and it is the dimer of PER/TIM that represses transcription of time and per
oscillations caused due to repression of tim and per
Around 4 am high levels of PER/TIM shut off per and tim, so PER/TIM level gradually fall. Then per and tim are no longer repressed, rise to a peak in late evening, leading to another peak in PER/TIM next morning at 4 am.
If either PER or TIM is absent nether one oscillates
genes - clock (clk) and cycle (cyc)
clk codes a protein CLK, and cyc codes CYC. In the daytime, the dimer CLK-CYC binds DNA and stimulates transcription of per and tim
what positive transcription factors do PER/TIM block
In the night, PER/TIM blocks CLK-CYC binding to DNA, and so represses transcription of per and tim.
doubletime (dbt) gene
Translation is a quick process, so we might expect PER and TIM levels to per and time by only a short interval, which would result in a cycle much shorter than 24 hours. But the protein DBT binds PER, causing it to breakdown, so the levels of PER rise much more slowly than they otherwise would, and so they do not peak until 6 hours after per, resulting in an overall cycle length near 24 hours.
in mammals, what does PER form a dimer with
PER forms a dimer not with TIM but with a protein called CRY from the cryptochrome or cry gene.
mamallian homologs of clk, cyc and dbt
clk, bmal1, and ck1epsilon
in mice and other mammals, a __________ dimer stimulates of _________ when not blocked by ________
_______ slows the rise of ______ protein levels.
in mice and other mammals, a CLK/BMAL1 dimer stimulates transcription of per and cry when not blocked by PER/CRY. CLK1epsilon slows the rise of PER protein levels.
zeitgeber
externals factors that internal clocks are kept in sync by (eg. light, temperaturem feeding, exercise and social interaction)
whats the main zeitgeber
light
what is the main zeitgeber sensed by and what does it project to
melanopsin and it projects to the master clock: the suprachiasmatic nucleus (SCN) of the hypothalamus
where does suprachiasmatic nucleus sit
above the optic chiasm
how are cellular clocks in the SCN reset
they are reset by light
signals from melanopsin retinal ganglion cells reach certain neurons in the SCN, making them fire and resetting their clocks by a small amount; the retinal signals cause chemical changes in these SCN cells that lead to a breakdown of PER/CRY
is this drop in PER/CRY occur after 4am, when PER/CRY levels are already falling, then it sets the clock forward a little, if it happens in the evening, when PER/CRY levels are rising, it sets the clock back.
what happens when there is light from 6-6:30 sm
Accelerates the breakdown of PER/CRY, reducing it to a level it would otherwise have reached a little, i.e. the clock is now running a little ahead.
from where does informaton about light and dark spread throughout the body
from the SCN
how does the SCN spread infromation
The SCN neurons that receive retinal projections send signals onward to other neurons in the SCN, so their intracellular clocks are adjusted as well.
From there, neural signals pass to other brain areas, which in turn send neural and hormonal signals that adjust the intracellular clocks throughout he body
entrainment
the process of nudging a clock into synchrony with another rhythm. So the SCN becomes entrained to night and day, and other clocks are entrained to the SCN and through it to night and day.
what does the pineal body release in darkness
melatonin
how do SCN neurons project to pineal body
SCN neurons project via other hypothalamic nuclei and then the sympathetic nervous system, to the pineal body, at the back of the diencephalon.
when does melatonin get released
the pineal gland releases the darkness hormone - melatonin- more in darkness and less in light. Starting at dusk, blood levels rise 8 fold, peaking at 2am, and then fall back to daylight levels by 8am
what does melatonin act via
it acts via melatonin receptors in the SCn to reset the master clock toward night time
where is the pineal gland
diancephalon
what happens in jet lag
the SCN master clock adjust itself gradually to the new schedule of light and dark, but only by one hour per day
how do melatonin pills help with jet lag
melatonin pills can help if they are taken correctly, i.e. for eastward travel, 30 minutes before your target bedtime at your destination
chronotypes within species
human early birds and night owls
why did chronotypes evolve
for the security of the herd, because they shorten the time when everyone is asleep
orexin - sleep
in daylight, the SCN indirectly excites neurons in the lateral hypothalamus, so they release orexin, causing arousal. loss of arousal causes narcolepsy.
melanin-concentrating hormone
in darkness, other cells in the LH are active, they project throughout the brain, releasing the neuropeptide melanin-concentrating hormone and inducing sleep.
orexin and MCH neurons relationship
orexin neurons and MCH neurons inhibit each other.
why do we feel sleepy
while we are awake, breakdown of ATP in the brain causes a buildup of adenosine, making us sleepy. During sleep, ATP levels are restored and adenosine levels fall.
what happens when we drink caffeine
caffeine blocks adenosine receptors but does not lower adenosine levels, so when the caffeine wears off, we crash
half-life of caffeine
it has a half life of 6 hours, its blood level is halfed in 6h, falls to 1/4 in 12h, 1/8 in 18h, etc
REM sleep
rapid eye movement sleep.
eyes move, dream, erratic 30-40Hz brain waves and muscle tone vanishes so you don’t act out your dreams
who has REM sleep
only birds and mammals have REM sleep, and aquatic mammals such as dolphins lack it, because without muscle tone they would drown, seals have REM sleep on land but not in the water.
non-REM sleep
its dreamless, with slower brain waves. It has three stages numbered 1-3, where Stage 3 is deep NREM, with regular 2-4 Hz brain waves.
in what cycle do stages of sleep follow each other
90 minute cycle
The first REM stage occurs after about 90 minutes. As the night progresses, sleep gets shallower and REM stages longer, and you may wake up occasionally.
why do we need sleep
for good cognitive function
what does deprivation of sleep, OR even just REM sleep cause
problems with cognitive function, learning and memory
what happens after sleep deprivation
after sleep deprivation, your first sleep will catch up on NREM, but the next few nights will have more REM than usual
comparison of human sleep with other primates
sleep with more REM and on the ground, rather than up a tree
