Neurobiology of circadian system Flashcards
Why does every tissue in human body contains in itself a 24h cycle?
To create an OPTIMAL environment for health
What did silk moth investigations show us about the clock?
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.
What was the ambiguity in silk moths experiments, when removing the brain showed a loss of regularity in behaviour?
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
What evidence did Truman (1970) find supporting the brain’s role in clock regulation?
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
There is evidence suggesting that we have 2 clocks
T/F
TRUE - Page (1982), found that only one optic lobe was necessary for having period
Menaker investigated avian circadian systems with 3 experiments________
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
Gaston was responsible for finding ______ core structure in circadian system. He demonstrated by____
PINEAL GLAND - secretes melatonin.
Ablation of it = arrythmicity BUT can be restored if strong D/N cycles
Transplanting the pinneal gland results in host organism________
inheriting the donors PHASE (time of day), not period
Period transport requires transplant of _______ whereas phase transplant requires moving _________
Period - brain
phase - pineal gland
Takahashi found that _________ structure is important for expressing overt circadian rhythms in sparrows
Superchiasmatic nucleus (SCN) because sends signals to pineal gland (melatonin) about incoming light = determines behaviour
Describe the pathway of light in circadian organisation in birds
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)
Melatonin is send back to the SCN because this structure is_____________
rich in melatonin receptors
Melatonin is the major indicator of the clock in all humans _________
Yes, except quadriplegia - don’t have any measurable melatonin
The superchiasmatic nucleus (SCN) is located;
a) occipital lobe
b) temporal lobe
c) cerebellum
d) hypothalamus
D - hypothalamus structure
We have ___ SCN’s which
a) 1
b) 2
c) 3
d) 4
B - 2 one for each hemi
The SCN receives input from both contralateral eyes
T/F
False - because it is so close to the optic chiasm (cross over between optic nerves) it receives input from both
Describe some evidence for the role of SCN in MAMMAL systems;
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)
Light is received in the;
a) core of the SCN
b) shell of the SCN
c) dorsomedial scn
d) extra occular photo receptors
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
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
A + D are true
SCN is a structure with many cells + many jobs
SCN has VIP and AVP cells
Describe the pathway of SCN input from the retina
Light enters eye –> retino-hypothalamic tract –> release of glutamate + PACAP –> SCN core –> SCN shell
SCN relies on ______ NT
a) glutamate
b) DA
c) 5-HT
d) GABA
D - GABA
The 3 major structures giving input to SCN are;
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)
Which structures in the brain stem interact with circadian system and release 5-HT?
Median raphe + dorsal raphe. Boost the clock’s sensitivity to light
IGL releases _________in to the SCN
Neuropeptide Y + GABA
The SCN has many outputs, all of which are needed for 24h clock maintenance
T/F
FALSE
What did Silver et al. contribute to knowledge of the SCN
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
The type of light we get exposed to matters for our circadian system, how was this measured?
Measuring melatonin suppression when exposed to different wavelengths of light
During day, rods and cones are most sensitive to______ light whereas circadian system is most sensitive to _____light
green/yellow
blue
visual photoreceptors that are he primary feeders of the circadian clock T/F
False, is MELANOPSIN
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
A - true 0.3% of retinal ganglion cells express melanopsin and they ALSO have direct input to other brain areas assoc with the clock
Intrinsically photoreceptive retinal ganglion cells (ipRGC’s) are
Retinal cells containing melanopsin
A mouse without melanopsin but rod and cone vision can still have D/N entrainment - WHY?
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
How do ipRGC behave different from normal photo receptors?
idRGC only serves to determine light/dark cycles, not sensitive to dim light.
when it turns ON, takes long time to turn off
Shining red and blue light, both with 100 lux intensity will produce the same pillilary response (T/F)
False - blue will cause MORE constriction than red light
We need experience of 24h rhythm to acquire it
False - dropshila flies riased in total light, then placed in darkness showed immediate 24h cycles without ever experiencing them
Describe the evidence suggesting that clocks are genetic?
Different periods have different FREE RUNNING periods
How are rhtyhms regulated in cells?
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
The NEGATIVE elements in the regulatory feedback loop are_________
Cryptochrome + period
Explain how phase shifting is achieved at the genetic level
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
We have maximum per activation during________
during day - max light
