Module 10

Question 1

How did David Walshe contribute to our understanding of biological clocks?

Answer 1

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

Question 2

What does tetrodotoxin do to individual neurons in the SCN?

Answer 2

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

Question 3

What did Seymour Benzer do?

Answer 3

Mutated flies until he found some with tau much greater than or less than 24h, or no rhythm at all

Question 4

What is the transcription-translation feedback loop?

Answer 4

PER protein may feed-back to inhibit the activity of the per gene

Question 5

The optic nerves cross over at the ______, and become _____

Answer 5

• optic chiasm

- optic tracts

Question 6

The optic nerves cross over at the ______, and become _____

Answer 6

• optic chiasm

- optic tracts

Question 7

When activated, the per gene generates ______, which is transferred from the _____ to the _____, where it is translated into ______

Answer 7

• permessenger RNA
• cell nucleus
• cytoplasm
• PER protein

Question 8

Per RNA peaks _____ before PER protein

Answer 8

6 hours

Question 9

Which proteins are transcriptional activators?

Answer 9

CYC and CLOCK

Question 10

The primary negative feedback loop involves _________, which form partners and return to_____, where they turn off ______ by _______

Answer 10

• PER and TIM
• the nucleus of the cell
• the transcription of their own genes
• interfering with CLOCK and CYC

Question 11

When the activation of CLOCK and CYC is blocked, _______, causing _____ and ______

Answer 11

• 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

Question 12

What happens if there is no PER or TIM left?

Answer 12

They no longer block CLOCK and CYC, which can then activate the per and tim genes again

Question 13

What does the gene doubletime do?

Answer 13

Codes for the protein DBT, an enzyme that modifies PER by attaching a phosphate group to it, marking it for degradation

Question 14

What are clock-controlled genes?

Answer 14

The genes that are directly regulated by cycling clock genes

Question 15

In flies, light causes degradation of ____, which normally rises during the ____

Answer 15

• TIM

- night

Question 16

In flies, light in the early night causes ______, explaining _____, and late at light night causes _____, explaining _____

Answer 16

• 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

Question 17

Exactly how does light affect clock genes?

Answer 17

Activates photoreceptor cells, which release glutamate, which activates the per gene

Question 18

In mammals, light in the early night ______, explaining _____, and late at light night _____, explaining _____

Answer 18

• 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

Question 19

The SCN in rodents contains _____ neurons on each side, the majority of which are _____

Answer 19

• 8000

- circadian clock cells

Question 20

The SCN, as a clock for the rest of the organism, does not work unless ______

Answer 20

-the individual clock cells are coupled with each other

Question 21

In constant bright light, the free-running circadian rhythms of nocturnal animals ____

Answer 21

Gradually damp out

Question 22

How does aging affect circadian rhythms of mice?

Answer 22

Weakens rhythms by weakening the degree of phase synchrony of clock cells

Question 23

What is most likely the cause of splitting?

Answer 23

Desynchrony between activity of the two SCN sides

Question 24

What is a neural explanation for jetlag?

Answer 24

The VL section of the SCN gets light input directly and shifts immediately, while the DM section shifts gradually

Question 25

What are the two parts of the SCN?

Answer 25

Dorsomedial and ventrolateral

Question 26

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?

Answer 26

• Single: Bmal1

- Pairs: Cry1 & Cry2, Per1 & Per2

Question 27

What did John O’Neill and Akilesh Reddy discover in 2011, and what are the implications?

Answer 27

• Circadian rhythms are present in mammilian cells that have no DNA
• These cells must differ from the standard transcription-translation feedback loop

Question 28

Where in the body does there seem to be oscillators?

Answer 28

Every organ and tissue

Question 29

What happens to luciferase expression under control of circadian clock genes?

Answer 29

Drives production of bioluminescence that can be measured in many tissues and brain regions

Question 30

In most brain areas that oscillate, the timing of the rhythm is _____

Answer 30

Opposite to that of the SCN

Question 31

Which non-SCN brain region shows the most robust circadian clock?

Answer 31

Olfactory bulb

Question 32

What is the dominant circadian time cue in peripheral tissues?

Answer 32

Meal time

Question 33

In a nocturnal mouse, feeding during the day causes the stomach and colon circadian rhythms to shift by ____

Answer 33

~12h

Question 34

The SCN doesn’t entrain to feeding schedules if _____

Answer 34

It is already entrained to a LD cycle

Question 35

In mice, knockout of Bmal1 does not affect _____

Answer 35

Food-entrained rhythms

Question 36

In rats and mice, feeding schedules must be between ______ to induce FAA

Answer 36

23h-29h

Question 37

How does the knockout of Bmal1 affect FAA in mice?

Answer 37

Bmal1KO mice can anticipate meals at any schedule, not just circadian ones

Question 38

There is a positive loop involving ______ and a negative loop involving _____

Answer 38

• clock and cyc

- per and tim

Question 39

Tim in rats corresponds with ____ in mammals

Answer 39

Cry1, Cry2

Question 40

cycle in rats corresponds with _____ in mammals

Answer 40

Bmal1, Bmal 2

Question 41

DBT in rats corresponds with _____ in mammals

Answer 41

CK1

Question 42

In the mamillian feedback loop, which genes are partnered or single?

Answer 42

Partners: clock/bmal1, per/cry
Single: rev-erb, ck1