Module 10 Flashcards
How did David Walshe contribute to our understanding of biological clocks?
He found a way to isolate single SCN cells and found that their activity peaked at different times and free ran, meaning they each had their own clock
What does tetrodotoxin do to individual neurons in the SCN?
Inhibits action potentials until it is washed off - afterwards, the rhythm of the neuron persists as if it oscillated even when no action potentials were firing
What did Seymour Benzer do?
Mutated flies until he found some with tau much greater than or less than 24h, or no rhythm at all
What is the transcription-translation feedback loop?
PER protein may feed-back to inhibit the activity of the per gene
The optic nerves cross over at the ______, and become _____
- optic chiasm
- optic tracts
The optic nerves cross over at the ______, and become _____
- optic chiasm
- optic tracts
When activated, the per gene generates ______, which is transferred from the _____ to the _____, where it is translated into ______
- permessenger RNA
- cell nucleus
- cytoplasm
- PER protein
Per RNA peaks _____ before PER protein
6 hours
Which proteins are transcriptional activators?
CYC and CLOCK
The primary negative feedback loop involves _________, which form partners and return to_____, where they turn off ______ by _______
- PER and TIM
- the nucleus of the cell
- the transcription of their own genes
- interfering with CLOCK and CYC
When the activation of CLOCK and CYC is blocked, _______, causing _____ and ______
- The per and tim genes stop being transcribed
- Synthesis of new PER and TIM to slow down
- The remaining PER and TIM is gradually removed by catabolic enzymes
What happens if there is no PER or TIM left?
They no longer block CLOCK and CYC, which can then activate the per and tim genes again
What does the gene doubletime do?
Codes for the protein DBT, an enzyme that modifies PER by attaching a phosphate group to it, marking it for degradation
What are clock-controlled genes?
The genes that are directly regulated by cycling clock genes
In flies, light causes degradation of ____, which normally rises during the ____
- TIM
- night
In flies, light in the early night causes ______, explaining _____, and late at light night causes _____, explaining _____
- TIM levels to be set back to what they were earlier in the day
- phase delays
- TIM levels to where they are later in the day
- phase advances
Exactly how does light affect clock genes?
Activates photoreceptor cells, which release glutamate, which activates the per gene
In mammals, light in the early night ______, explaining _____, and late at light night _____, explaining _____
- raises PER levels to what they were earlier in the day
- phase delay
- raises already-rising PER levels to what they would be later in the day
- phase advance
The SCN in rodents contains _____ neurons on each side, the majority of which are _____
- 8000
- circadian clock cells
The SCN, as a clock for the rest of the organism, does not work unless ______
-the individual clock cells are coupled with each other
In constant bright light, the free-running circadian rhythms of nocturnal animals ____
Gradually damp out
How does aging affect circadian rhythms of mice?
Weakens rhythms by weakening the degree of phase synchrony of clock cells
What is most likely the cause of splitting?
Desynchrony between activity of the two SCN sides
What is a neural explanation for jetlag?
The VL section of the SCN gets light input directly and shifts immediately, while the DM section shifts gradually
What are the two parts of the SCN?
Dorsomedial and ventrolateral
What are the single gene and pairs of genes that, when knocked out of a mouse, ensures the mouse cannot sustain a circadian rhythm in constant conditions?
- Single: Bmal1
- Pairs: Cry1 & Cry2, Per1 & Per2
What did John O’Neill and Akilesh Reddy discover in 2011, and what are the implications?
- Circadian rhythms are present in mammilian cells that have no DNA
- These cells must differ from the standard transcription-translation feedback loop
Where in the body does there seem to be oscillators?
Every organ and tissue
What happens to luciferase expression under control of circadian clock genes?
Drives production of bioluminescence that can be measured in many tissues and brain regions
In most brain areas that oscillate, the timing of the rhythm is _____
Opposite to that of the SCN
Which non-SCN brain region shows the most robust circadian clock?
Olfactory bulb
What is the dominant circadian time cue in peripheral tissues?
Meal time
In a nocturnal mouse, feeding during the day causes the stomach and colon circadian rhythms to shift by ____
~12h
The SCN doesn’t entrain to feeding schedules if _____
It is already entrained to a LD cycle
In mice, knockout of Bmal1 does not affect _____
Food-entrained rhythms
In rats and mice, feeding schedules must be between ______ to induce FAA
23h-29h
How does the knockout of Bmal1 affect FAA in mice?
Bmal1KO mice can anticipate meals at any schedule, not just circadian ones
There is a positive loop involving ______ and a negative loop involving _____
- clock and cyc
- per and tim
Tim in rats corresponds with ____ in mammals
Cry1, Cry2
cycle in rats corresponds with _____ in mammals
Bmal1, Bmal 2
DBT in rats corresponds with _____ in mammals
CK1
In the mamillian feedback loop, which genes are partnered or single?
Partners: clock/bmal1, per/cry
Single: rev-erb, ck1
