Neurobiology of circadian system

Question 1

Why does every tissue in human body contains in itself a 24h cycle?

Answer 1

To create an OPTIMAL environment for health

Question 2

What did silk moth investigations show us about the clock?

Answer 2

Removing the brain caused them to STOP being regular in the time that they left their casing = introduced idea that brain is involved in rhythms.

Question 3

What was the ambiguity in silk moths experiments, when removing the brain showed a loss of regularity in behaviour?

Answer 3

a) did it mean that the brain = loss of all clock function
b) did it mean that the clock remained active BUT it cold no longer communicate with other cells/organs and therefore could not affect behaviour

Question 4

What evidence did Truman (1970) find supporting the brain’s role in clock regulation?

Answer 4

did a PERIOD TRANSPLANT, implanted donor brain into organism, this organism (receiver) then had the same period as the donor = brain > body in clock

took out cockroaches eyes, began FREE RUNNING - still had regular period just not mediated by external cues. Took out OPTIC LOBES = arrhythmic.
= brain role > body

Question 5

There is evidence suggesting that we have 2 clocks

T/F

Answer 5

TRUE - Page (1982), found that only one optic lobe was necessary for having period

Question 6

Menaker investigated avian circadian systems with 3 experiments________

Answer 6

1) took out sparrow eyes, could still entrain BUT LATER started free running
2) took out some feathers from the birds head, REGAINED ability to entrain bc scalp is thin = permeable to light therefore could detect d/n cycle
3) Injecting ink under the scalp = started free running again bc light can’t penetrate the scalp = DEEP BRAIN PHOTORECEPTORS // extra-ocular photo receptors

Question 7

Gaston was responsible for finding ______ core structure in circadian system. He demonstrated by____

Answer 7

PINEAL GLAND - secretes melatonin.

Ablation of it = arrythmicity BUT can be restored if strong D/N cycles

Question 8

Transplanting the pinneal gland results in host organism________

Answer 8

inheriting the donors PHASE (time of day), not period

Question 9

Period transport requires transplant of _______ whereas phase transplant requires moving _________

Answer 9

Period - brain

phase - pineal gland

Question 10

Takahashi found that _________ structure is important for expressing overt circadian rhythms in sparrows

Answer 10

Superchiasmatic nucleus (SCN) because sends signals to pineal gland (melatonin) about incoming light = determines behaviour

Question 11

Describe the pathway of light in circadian organisation in birds

Answer 11

1) Light enters light
2) Reaches deep brain photo receptors
3) Info transmits to SCN
4) info goes to superior cervical gnaglion (SCG)
5) Info goes to pineal gland (melatonin sent to general circulation via spinal cord AND back to the SCN)

Question 12

Melatonin is send back to the SCN because this structure is_____________

Answer 12

rich in melatonin receptors

Question 13

Melatonin is the major indicator of the clock in all humans _________

Answer 13

Yes, except quadriplegia - don’t have any measurable melatonin

Question 14

The superchiasmatic nucleus (SCN) is located;

a) occipital lobe
b) temporal lobe
c) cerebellum
d) hypothalamus

Answer 14

D - hypothalamus structure

Question 15

We have ___ SCN’s which

a) 1
b) 2
c) 3
d) 4

Answer 15

B - 2 one for each hemi

Question 16

The SCN receives input from both contralateral eyes

T/F

Answer 16

False - because it is so close to the optic chiasm (cross over between optic nerves) it receives input from both

Question 17

Describe some evidence for the role of SCN in MAMMAL systems;

Answer 17

1) location - it is in optimal location receive light input adjacent to optic chiasm branching off retina
2) Transplantation - transplanting it into an ARRHYTHMIC animal = gives them rhythmicity
3) isolation - creating ‘SCN islands’ and cutting it off from all other brain structures showed substantia nigra did NOT have rhythms but island DID = can independently CREATE rhythms (Inouye & Kawamura)
4) Explantation - removing SCN from body did not stop it from working
5) Ablation - removing it from organism - made it arrhythmic (Stephen Zucker)

Question 18

Light is received in the;

a) core of the SCN
b) shell of the SCN
c) dorsomedial scn
d) extra occular photo receptors

Answer 18

A - light is recieved in the CORE (ventralateral SCN) and then gets transmitted to the shell (dosromedial SCN)

i.e. starts of DEEP and then signals sprouts outwards

Question 19

SCN is a structure with many cells + many jobs
SCN is a structure with few cells + many jobs
SCN has homogenous organisation
SCN has VIP and AVP cells

Answer 19

A + D are true
SCN is a structure with many cells + many jobs
SCN has VIP and AVP cells

Question 20

Describe the pathway of SCN input from the retina

Answer 20

Light enters eye –> retino-hypothalamic tract –> release of glutamate + PACAP –> SCN core –> SCN shell

Question 21

SCN relies on ______ NT

a) glutamate
b) DA
c) 5-HT
d) GABA

Answer 21

D - GABA

Question 22

The 3 major structures giving input to SCN are;

Answer 22

1- Thalamus / IGL (GHT tract, important for NOCTURNAL animals, gets activated when they are active in DAY)
2 - Retina (retinohypothalamic (RHT) tract)
3 - Brain stem / MRN ( D/M raphe)

Question 23

Which structures in the brain stem interact with circadian system and release 5-HT?

Answer 23

Median raphe + dorsal raphe. Boost the clock’s sensitivity to light

Question 24

IGL releases _________in to the SCN

Answer 24

Neuropeptide Y + GABA

Question 25

The SCN has many outputs, all of which are needed for 24h clock maintenance
T/F

Answer 25

FALSE

Question 26

What did Silver et al. contribute to knowledge of the SCN

Answer 26

Transplanted infant SCN inside a POROUS capsule i.e. could NOT form neural connections. STILL was able to give host organism the donor’s behavioural rhythms

= there was something diffusing out of SCN/capsule pores that enabled organism to inherit rhythm

= epidermal growth factor

Question 27

The type of light we get exposed to matters for our circadian system, how was this measured?

Answer 27

Measuring melatonin suppression when exposed to different wavelengths of light

Question 28

During day, rods and cones are most sensitive to______ light whereas circadian system is most sensitive to _____light

Answer 28

green/yellow

blue

Question 29

visual photoreceptors that are he primary feeders of the circadian clock T/F

Answer 29

False, is MELANOPSIN

Question 30

a) Melanopsin is expressed in .3% of all retinal ganglion cells
b) Melanopsin is expressed in .5% of all retinal ganglion cells
c) Melanopsin is expressed in .08% of all retinal ganglion cells
d) Melanopsin is expressed in the fovea only

Answer 30

A - true 0.3% of retinal ganglion cells express melanopsin and they ALSO have direct input to other brain areas assoc with the clock

Question 31

Intrinsically photoreceptive retinal ganglion cells (ipRGC’s) are

Answer 31

Retinal cells containing melanopsin

Question 32

A mouse without melanopsin but rod and cone vision can still have D/N entrainment - WHY?

Answer 32

Because rods and cones are also important for entrainment. Rods/cones can still project signal to the ipRGC (even if they don’t contain melanopsin) = influence downstream clock structures

Question 33

How do ipRGC behave different from normal photo receptors?

Answer 33

idRGC only serves to determine light/dark cycles, not sensitive to dim light.
when it turns ON, takes long time to turn off

Question 34

Shining red and blue light, both with 100 lux intensity will produce the same pillilary response (T/F)

Answer 34

False - blue will cause MORE constriction than red light

Question 35

We need experience of 24h rhythm to acquire it

Answer 35

False - dropshila flies riased in total light, then placed in darkness showed immediate 24h cycles without ever experiencing them

Question 36

Describe the evidence suggesting that clocks are genetic?

Answer 36

Different periods have different FREE RUNNING periods

Question 37

How are rhtyhms regulated in cells?

Answer 37

Negative feedback loop where;

a) clock and DNAL (pos elements) ACTIVATE
b) period and cryptochrome (neg elements)
c) produce proteins + RNA
d) ^^^ move back into the nucleus where they signal clock/DNAL to STOP producing more shit

Question 38

The NEGATIVE elements in the regulatory feedback loop are_________

Answer 38

Cryptochrome + period

Question 39

Explain how phase shifting is achieved at the genetic level

Answer 39

Light exposure = ACTIVATES per (regardless)
if light exposure early evening - per gets INCR = delay bc has to run that time length again to get back to prior level
if light exposure early morning - per ALSO gets INCR bc now it thinks that its already further in the day = advance

Question 40

We have maximum per activation during________

Answer 40

during day - max light