Circadian Rhythm Flashcards
Define circadian rhythm
Sustained oscillations with a period of approximately (but not exactly) 24 hours
What kinds of organisms have a circadian rhythm?
All! Everything from bacteria to mammals to plants
Why is circadian rhythm important?
Allows an organism to be more productive in its waking hours: e.g. do not want to be sleepy and hungry at the same time, if they are staggered we can take care of ourselves better
What are the 3 components of the biological clock?
- Input: a way to set the clock
- Oscillator: the clock itself
- Machinery: Helps allow the clock to control the activity of genes which need to be regulated
How were genes associated with circadian rhythm discovered in D. melanogaster?
Monitored eclosion (emergence of adult from pupa stage) and did genetic screening of adults which emerged at the “wrong” time (it is normally supposed to happen in the morning)
The SCN is part of this brain structure
The hypothalamus
The “oscillator” in human/mammal circadian rhythm is…
The SCN
Cells from this region in vitro can maintain 100% of their circadian rhythm
SCN neurons
What is the role of the SCN?
Send output to peripheral tissues to follow the body’s CR due to light cues
When a non-SCN cell is in isolation, what happens to its CR?
Maintain their rhythmicity given the medium is changed periodically, but the intrinsic rhythm does not respond to light cues
What TFs make up a heterodimer and bind to the Ebox element upstream of important circadian rhythm genes?
Clock and Bmal1
The Clock/Bmal1 heterodimer promotes the transcription of these genes (3)
- Period (Per)
- Cryptochrome
- Rev-erb alpha
Which is thought to be the most “important” of REV, Per, and Cry?
Per
How can expression of Bmal1 be inhibited?
REV acts on the DNA regulatory region for Bmal1 = negative feedback
Which complex inhibits the Clock/Bmal1 dimer?
Per/Cry complex
How is expression of Clock/Bmal1 reinitiated after inhibition by Per/Cry?
With Per/cry inhibition, Clock/bmal1 stop acting on their target genes, Less REV/Per/Cry activity, therefore there is less REV inhibiting clock and Bmal1 and less Per/Cry to inhibit the clock/bmal1 complex
The SCN has direct connections to this hormone-secreting gland which affects the sleep/wake cycle
The pineal gland
What is the main secretion of the pineal gland?
Melatonin
Melatonin is derived from…
Tryptophan
At what time of day is melatonin upregulated?
Night
To improve jet lag, when should one take melatonin during travel?
At the destination’s “dark” time
How is the circadian clock reset?
Light input coming from the retina to the SCN
The connection between the retina and the SCN is called the…
Retinal hypothalamic tract
The resetting of the oscillator by light is called…
Photoentrainment
During an assessment of locomotor activity, when mice with functional eyes (no enucleation) are put in several days of darkness, what happens to their CR?
Maintains rhythmicity but starts to become “skewed” - because rhythm is not quite 24h
The mouse circadian rhythm is (more/less) than 24h
Less
The human circadian rhythm is (more/less) than 24h
More
What is the primary function of ipRGCs?
Responsible for photoentrainment, project to SCN via retinohypothalamic tract
Describe the circadian rhythmicity of rd/rd mice. Why is it like this?
More or less the same as wt mice: because these mice still have ipRGCs
How can you get an rd/rd mouse to stop responding to circadian light cues?
Enucleation (removal of the eye :( )
When mice are enucleated, what are the 2 results?
- Loss of photoentrainment
- Loss of pupillary reflex
NMDA channels open in response to…
Glutamate
How are circadian clock genes activated?
Ganglion cells signal to target cells by releasing glutamate, which binds to NMDA channels causing them to open. Ca2+ enters the cell and activates CREB, which activates circadian clock genes (particularly Period)
Period is at its highest at (dawn/dusk) in mice
Dusk
A burst of light at dusk will (advance/delay) circadian activities
Delay
A burst of light at dawn will (advance/delay) circadian activities
Advance
