Circadian Rhythms

Question 1

How do the cycles of animals near equatorial regions and polar regions differ?

Answer 1

• Equatorial: based on day/night cycles (circadian rhythm)

- Polar: Seasonal cycles (circannual rhythm)

Question 2

What are the 4 types of biorhythms? Provide an example of each.

Answer 2

1. Circannual: Yearly (e.g., migration of birds)
2. Infradian: Less than a year (e.g., human menstrual cycle)
3. Circadian: Daily (e.g., human sleep cycle)
4. Ultradian: Less than a day (e.g., eating cycle)

Question 3

What processes are regulated by circadian rhythms?

Answer 3

• Sleep / wake
• Body temperature
• Blood flow
• Urine production
• Hormone regulation
• Metabolic rate
• Alertness
• Growth hormones
• Cortisol
• Potassium

Question 4

What are the 3 properties of circadian rhythms?

Answer 4

1. 24 hour period: Responses repeat on a roughly 24 hour period
2. Endogenous: Rhythmic responses continue in the absence of stimulation
3. Entrainable: Circadian rhythms can be reset or adjusted by exposure to external stimuli

Question 5

Is plant movement exogenous or endogenous?

Answer 5

• Leaves open up during the day for photosynthesis and close at night
• Endogenous behaviour: If a plant is placed in a constantly dim light and a pen is attached to the leaf to record when it moves, it will produce a rhythmic movement that occurs even in the absence of light

Question 6

How are circadian rhythms studied in mammals?

Answer 6

• Rat has access to a running wheel that is connected to a computer
• Computer measures amount of revolutions
• Produces attogram: Each line represents a day’s activity
• Rats are active when lights are turned off but scurry away when lights go on (decreased activity)

Question 7

What experiment with rats showed that circadian rhythms are entrainable?

Answer 7

• When attogram recorded rat activity when there were 12 hours with lights on and 12 hours with lights off, there was a predictable pattern of activity
• When rats were placed in constant darkness, there was still rhythmicity, but the animals’ behaviours ran a little slower. This is because the internal clock runs on about 24.5 to 25.5 hour cycles
• Eventually there is a reversal of behaviour where they are active during periods where they weren’t active and vice versa
• Circadian rhythms are endogenous but they are not perfect, so they must be entrained by other cues such as light

Question 8

What are zeitgebers?

Answer 8

• Means “time giver”
• Endogenous rhythms are not accurate enough to be 100% reliable
• Light entrains biological clocks to day/night cycle: Acts to “reset” the circadian clock to maintain its correspondence to the outside world
• A circadian clock that is properly reset by a zeitgeber is said to be entrained

Question 9

What is a free running rhythm?

Answer 9

• A circadian rhythm in the absence of zeitgebers that is a little more / less than 24 hours

Question 10

What did Aschoff and Weber’s bunker study show about circadian rhythms?

Answer 10

• When isolated from the sun, people’s free-running rhythms tended to be slightly longer than 24 hours
• Every night, tended to go to bed a bit later than the night before until sleep/wake cycle was completely reversed
• In some cases, physiology and behaviour become out of sync: When master clock gets out of sync, hormone release becomes out of sync with behaviour

Question 11

What are the 3 elements of a biological clock?

Answer 11

1. Light sensor: Senses changes in lightness / darkness (eyes); entrains the clock and keeps its rhythm coordinated with the environment
2. Clock: Continues to run and keeps a basic rhythm in the absence of any input
3. Output pathway: Allows clock to control brain and body functions (e.g., signalling to the adrenal glands to release cortisol)

Question 12

What is the suprachiasmatic nucleus?

Answer 12

• Region above the hypothalamus located above the optic chiasm
• Small cluster of neurons that serve as biological clock
• Receives information from light that comes into the eyes

Question 13

What happens when the SCN is lesioned?

Answer 13

• Abolishes circadian rhythmicity of physical activity, sleep/wake cycles, feeding, drinking, etc.
• Animals will sleep around the same amount but the distribution of sleep will be random
• SCN from another organism can be transplanted and rhythms will resume within 2-4 weeks (suggests rhythms are endogenous rather than learned)

Question 14

What is the retinohypothalamic tract?

Answer 14

• Axons from ganglion cells in the retina that synapse onto dendrites on SCN neurons. This input is required for entrainment, and SCN neurons are sensitive to light in non-selective way.
• Ganglion cells express a photopigment called melanopsin that is depolarized by light

Question 15

Where does the SCN output to?

Answer 15

• Nearby hypothalamic nuclei
• Midbrain and other parts of diencephalon
• GABAergic (inhibitory)
• Also use vasopressin
• Lesions to efferent SCN pathways disrupt circadian rhythms

Question 16

Explain the pathway that leads to the production of melatonin.

Answer 16

• SCN provides inhibitory tone to the PVN
• PVN projects to preganglionic sympathetic neurons in spinal column
• Preganglionic sympathetic neurons modulate neurons in pineal gland
• Pineal gland synthesizes melatonin from tryptophan
• Melatonin production goes up as environmental light goes down
• When secreted into bloodstream, melatonin binds to melatonin receptors on SCN neurons and influences sleep wake cycles (indicates lack of light)

Question 17

How do SCN neurons keep time?

Answer 17

• Raising SCN neurons in vitro demonstrates that they intrinsically keep time
• Rhythmicity of glucose utilization, protein synthesis, vasopressin production, etc. remains intact in absence of zeitgebers
• Rhythmicity also occurs after tetrodotoxin administration (doesn’t require APs between each other to maintain rhythmicity)

Question 18

What are clock genes of SCN neurons?

Answer 18

• Used to endogenously keep time
• Genes are transcribed and translated
• After a delay, proteins send feedback by interacting with transcription factors, causing a decrease in gene expression (negative feedback loop)
• Less protein production, less inhibition of gene expression and eventually the cycle renews in 24 hours

Question 19

What are the names of clock genes / proteins?

Answer 19

1. Cryptochrome (CRY)
2. circadian locomotor output cycles kaput (CLOCK)
3. Brain and muscle ARNT-like (BMAL1)
4. Period (PER1, PER2, PER3)

Question 20

Explain the negative feedback loop of clock genes.

Answer 20

• BMAL1 and Clk translated into proteins and form heterodimer C-B
• C-B re-enters nucleus and promotes transcription of other genes while inhibiting others
• CRY-PER2 heterodimer goes back into nucleus and promotes transcription of BMAL1 and Clk and cycle continues

Question 21

What are the 3 key components of the feedback loop of clock genes?

Answer 21

1. Concentration of BMAL and 3 PER proteins cycle in counterphase
2. PER2 is positive regulator of BMAL1 loop
3. CRY is negative regulator of the period and cryptochrome loops (shuts system down)