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.
