Circadian

Question 1

What is the most powerful entrainment stimulus of the circadian rhythm?

Answer 1

Light-dark cycle (zeitgeber)

Once entrained to a zeitgeber, circadian rhythms can persist in its absence, but the timing is not precise

Question 2

Where is the master circadian clock located?

Answer 2

Suprachiasmatic nucleus (SCN) of hypothalamus

Question 3

What happens when you lesion SCN?

Answer 3

abolish rhythms of activity, hormone secretion, body temperature, etc. and result in desynchrony of peripheral circadian oscillators;
transplantation of SCN into hypothalamus of SCN lesioned animals restores rhythms with the phase of the donor‑encapsulated transplants;
explanted SCN demonstrate persistent circadian
rhythms of neuronal activity, glucose utilization and
gene expression

Question 4

What are the essential components of a circadian system?

Answer 4

1. Zeitgeber
2. Receptor
3. Input signal transduction
4. Rhythm generator
5. Output signal transduction
6. Output rhythm

Question 5

What happens to mice with an optic nerve transection?

Answer 5

Lose the ability to reset the clock

Question 6

What is experimental evidence that blind mice can still perceive light?

Answer 6

1. Their circadian rhythm still shifts after being exposed to a different light/dark cycle
2. Their pupils still dilate after being exposed to light
3. They freeze during the night when a light is shined on them

Question 7

What cells are responsible for light perception when cones/rods are gone?

Answer 7

Intrinsically photosensitive ganglion cells (ipRGCs)

project directly to SCN;
mediated by vision but not about seeing;
consist 5% of the photoreceptor;
main function to detect when the light is on/off;
contain melanopsin

Question 8

What happens when cones and rods only are degenerated?

Answer 8

Light can still shift the phase of the clock

Question 9

hierarchical organization of body clocks

Answer 9

lesion of SCN, rhythm still exist in other organs but
desynchronized;

asynchronous phase‑shifting of peripheral oscillators: the meaning of jet‑lag

Question 10

What are the properties of Melatonin?

Answer 10

1.Synthesized/released at night; light suppresses
release
2.Provides time of day info to SCN and peripheral
clocks
3 regulate seasonal breeding in animals
4 facilitates sleep
5 anti‑oxidant properties
6 improve immune function
7 decreases growth of cancer cells

Question 11

Describe experiment that shows that circadian clocks alter cancer progression

Answer 11

In mice with cancer, SCN lesions cause the tumor to be bigger and cause the mice to die faster.

shift work
disrupts circadian rhythms
suppresses immune function
suppresses nocturnal melatonin release

Question 12

retinal dopamine

Answer 12

1 synthesized and release from amacrine and
interplexiform cells
2 stimulated by light and modulated by circadian
clocks
3 retinal dopamine neuron express circadian clock
genes and have been suggested to regulate light adaptive retinal function
4 retina expresses 4 subtypes of dopamine receptors, D1, D2, D4 and D5, all are GPCRs
5 after release, dopamine diffuses throughout the
retina
6 D4 are highly expressed in the retina

Question 13

describe the vertebrate retina as a circadian system

Answer 13

1 widespread molecular rhythms generation
2 light entrainment involving dopamine
3 output pathway regulates function (ERG,OKT)
4 melatonin biosynthesis and release from
photoreceptor cells
5 dopamine release from amacrine/interplexiform cells

Question 14

What photopigment is responsible for non-visual photoreception? Evidence (2)?

Answer 14

Melanopsin.

1. Mice with cone/rod/Melanopsin KO fail to entrain to a light-dark cycle.
2. Triple KO mice have no pupillary eye reflex

Question 15

neuromodulators of light and dark adaptation

Answer 15

melatonin: dark‑adaptive physiology
dopamine: light‑adaptive physiiology

Dopamine inhibits melatonin during the day
(melatonin active during NIGHT)
Melatonin inhibits dopamine during the night (dopamine active during DAY)

Question 16

Experiment demonstrating that dopamine modulates circadian rhythms of rodcone
dominance

Answer 16

Cone activity typically highest during day. Rod
activity highest at night. Give D2 agonist (quinpirole) at night – cones become active even
though it’s night. Give D2 antagonist (eticloperide)
during day – rods become active even though it’s
day

Question 17

role of retinal dopamine (2 experiments) and which

receptor involved

Answer 17

generation of retinal specific Th gene disruption;
reduced amplitude of the ERG rhythm in retinal
dopamine deficient mice;
D4R modulate circadian

Question 18

visual acuity vs contrast sensitivity

Answer 18

behavior task: optokinetic tracking

Question 19

what regulate visual acuity/sensitivity

Answer 19

circadian regulation of contrast sensitivity, but
not acuity;
dopamine modulate both;
D1 for acuity, D4 for contrast sensitivity;
CLOCK gene is necessary for the contrast sensitivity

Question 20

functions of retinal melatonin

Answer 20

1. synthesized primarily by photoreceptors
2. modulates synaptic transmission in the inner
   retina
3. promotes rod dominant night vision by shifting the balance of rod‑cone input to second order neurons to a rod dominant state
4. acts on GPCR: MT1 and MT2 receptor that promote dark adaptation
5. exp: diurnal rhythm of dark‑adapted EFG in wild type, but not in MT1 receptor deficient mice