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- High during the day
- Low at night
- Excretion of waste
- High during the day
- Low at night
- Jump when you wake up, helps you get going
- From adrenal glands
- Decreases throughout the day
- High when you sleep
- Low during the day
Purpose of Kleitman and Richardsons cave experiment?
- 33 day experiment
- Determined whether the human body-clock can be adjusted
What are the features of circadian rhythms?
- Period of 24 hours is roughly maintained
- Rhythm persists in absence of external cues
- Can be entrained with light
- Rhythm maintained over a range of temperatures (body tem controlled by metabolism)
What is a common feature throughout phylogeny?
- Circadian rhythms
- Bacteria colony growth
- Opening/closing of mimosa leaves
- Diurnal and nocturnal animals
How does a protein synthesis inhibitor affect the rhythm of the clock?
- Inhibitor stops clock
- Different from covering clock
- Remove inhibitor and clock starts again from where it left off
What is the key molecular component for the clock?
What happens when there is a mutation in the period gene per locus?
What causes arrhythmic activity?
A mutation in the period gene per locus
What does SCN stand for?
Where is the SCN located?
- Neuroendocrine center
- Sits right above optic chiasm
What is an optic chiasm?
Where optic nerves/RGC cross
What is the SCN?
- Suprachiasmatic Nucleus
- Master circadian clock in mammals
What kind of input does the SCN receive? From where?
- a. Axon projections
- b. Retina
Why does the SCN receive input from the retina?
Want clock to be entrainable by visible input coming in
How do we know the SCN is necessary?
- Lesion/knock it out, lose normal activity rhythms; prevents entrainment
- Transplant it back, regains consistent rhythm, though augmented
How do we know the SCN is sufficient?
- Lack of it = arrhythmic activity
- Presence (even from a donor) = restore rhythmicity
- Cultured brain slices containing SCN maintained rhythmicity
- Isolated SCN neurons also maintain rhythmicity
What happens over time with isolated SCN neurons?
- Go out of sync with one another
- Individual neurons express their own rhythms
- Dont communicate with other cells
How can we visually see activity in the brain?
- Using GFP (fluorescent signal)
- Glows green during the day, breaks down with rhythm
What drives the expression of GFP in the SCN?
The promoter for Per 1
Is the SCN the only cell type that has circadian clocks?
- No, lots of cells express clock/rhythm
- But not important for driving behavior
- Ex. Liver and kidney work at diff times
How is the clock entrained by light?
From intrinsically photosensitive Retinal Ganglion Cells (IpRGCs)
What does IpRGC stand for?
Intrinsically photosensitive Retinal Ganglion Cells
What happens when we remove eyes?
Rhythm is gone
How do we know its not just the rods and cones telling us about light in the environment?
If we remove them, can still entrain circadian rhythms to light
How do we know that its the Retinal Ganglion Cells (RGCs) that respond to light?
- Inject fluorescent beads into retina that label the SCN
- Or inject retro-beads into the SCN that dyes/labels some RGCs (opposite direction)
- Even after synapses are blocked w/ an antagonist, they continue to respond to light
- Therefore, signal isnt from photoreceptor cells. Theyre from RGCs themselves
How do IpRGCs respond to light?
What is melanopsin?
Protein similar to rhodopsin
What happens when the melanopsin gene/protein is knocked out?
RGCs lose their light-sensitivity
What are PER and TIM?
Proteins named Period and Timeless
When are PER and TIM transcribed and translated?
Early morning and throughout afternoon
What happens to PER and TIM during the evening time?
- There is enough protein that they start to create heterodimers in the cytoplasm
How does the heterodimer PER/TIM affect the creation of individual PER and TIM proteins?
- Negatively regulates their creation
- Moves to the nucleus and shuts down their transcription
How is the repression of PER/TIM stopped?
- Blue light activates photoreceptor cryptochrome (CRY), which is associated with TIM
- Regulates TIMs degradation
- Stops repression and allows more transcription of individual PER and TIM proteins
- Restarts cycle
What must be done to fully stop entrainment?
What 3 things must be knocked out to fully stop entrainment?
- Transducin alpha-subunit (rods)
- CNG channels (cones)
- Melanopsin (IpRGC)