Circadian Rhythms Flashcards
What experiment figured out that we must have a central circadian clock?
- Had people sleep with and without cues a
- found that in the absence of cues humans still showed a sleep wake cycle, but the cycle was more than 24 hours (about 25 hrs)
What other daily cycles do we have besides sleep/wake? (3)
- Melatonin levels
- Body temp
- Serum control
Where is the central clock?
-In the SCN (suprachiasmatic nucleus)
How do we know where central clock is?
- neurons in the SCN fire action potentials in a 24 hour rhythm
- isolated SCN neurons continue to keep this rhythm
What happens during ablation of SCN?
disrupts wake/sleep cycle in mice
What happens if SCN is transplanted?
transplanted SCN confers time keeping of host to recipient
What is per?
-central component of the clock, which when mutated leads to altered circadian rhythms
Where were mutations in the central clock studied?
in flies
Where is per expressed?
in the SCN
How do per mRNA and protein cycle?
with a 24 hour rhythm (found in various levels throughout the day)
_____ peaks during the day, ____ peaks during the night
mRNA peaks during day, protein peaks during night
per is a ______ factor which means that it controls _______
- transcription
- expression of other genes
What do per and cry form? What is the function?
- heterodimer
- together they inhibit their own expression
What are per and cry turned on by?
- Bmal
- Clk
How is the central clock maintained?
a ~24 hr of cycle of per transcription, translation, degradation
-controlled by negative feedback of per on its own expression
What is the molecular clock composed of?
4 transcription factors in 2 transcriptional networks
What turn Per back on?
Clock + cycle
What does per do at night?
- enters nucleus
- blocks its own expression
What is the non-visual input to the SCN?
-retinal ganglion cells that express the visual pigment melanopsin can detect light (even in the absence of photoreceptor input)
What are the cells of the non-visual input to the SCN?
- intrinsically photosensitive RGCs
- (ipRGCs)
Where do Melanopsin cells/ipRGCs project? How is this determined?
- SCN
- by expressing lacZ gene
What does the lacZ gene generate?
-blue color under melanopsin promoter
What happens when you genetically kill melanopsin cells?
-animals lose entrainment to light
Does melanopsin KO produce the same results as genetically killing melanopsin cells?
- no
- ipRGC can also receive input from photoreceptors in abscence of melanopsin
What kind of cells are essential for circadian entrainment?
ipRGCs(melanopsin cells)
ipRGCs(melanopsin cells) are essential for ________
circadium entrainment
Where do ipRGCs synapse? what does this cause?
- synapse in SCN,
- cause change in IC signaling in SCN neurons
What happens if you add DT to selectively kill melanopsin cells
-loss of light entrainment
What is familial advanced sleep phase syndrome associated with?
- associated with mutation in the per gene
- causes it to accumulate more quickly
- shortening the clock
What is the definition of sleep? (4)
- naturally recurring state
- reduced/absent consciousness
- relatively suspended sensory activity
- inactivity of nearly all voluntary muscles
What is the pattern of sleep cycle?
- Sleep cycle is about 90 minutes
- Each cycle has longer REM stages
How many sleep stages?
5
What is REM?
- rapid eye movements
- dreaming, muscle paralysis
What is stage 4 of sleep?
- deepest sleep
- most restful (2 per night)
How was it shown that sleep is essential?
- take 2 rats and allow one to fall asleep and not the other
- The one that isn’t allowed to sleep dies and loses body weight
What is the sleep center and how is it activated and inactivated?
- If you stimulate the Reticular activating system the animal is awakened
- If you stimulate the thalamus the animal falls asleep.
What is the effect of antihistamines on sleep?
- cause sleepiness
- histamine is used as a neurotransmitter by a brain area that promotes arousal (TMN)
- if this is inhibited, sleep is promoted
What are 3 sleep disorders?
- Narcolepsy
- Sleep apnea
- Delayed sleep phase syndrome
What is narcolepsy?
- recurring short episodes of sleep accompanied by cataplexy-mutation in orexin receptor gene leads to narcolepsy in mice and dogs
- in humans it is thought to be an autoimmune response that leads to loss of orexin neurons
What is sleep apnea
obstruction of upper airways due to loss of muscle tones leads to frequent awakening
What is synaptic scaling?
-During day, synapses get potentiated (throughLTP)
What is the evidence of synaptic scaling?
found in 3 fruitflies that synapse size/number increases after a few hours of wake, decreases only if flies are allowed to sleep
Why do potentiated synapses need to be corrected?
-because larger synapses use more energy
