PTOs & Food Entrainment & MASCO Flashcards
What is used in circadian organization:
Between cells and tissues
Within cells
Between:
- Oscillator coupling, intercellular signalling
- Distribution of functions (e.g. light input, rhythm generation)
- Feedback of circuits from peripheral oscillators
Within:
- TTFL
- PTO
Oscillator coupling
Circadian blindness
Set of organs work together and share responsibility to produce circadian cycle
- Important to have backup if something fails
- SCN must also receive feedback from other oscillators around body (not always needed)
Must have no eyes at all to be circadian blind
- Diff from visual blind (which is reliance on photoreceptors)
How do plant clocks differ from animal clocks? Conflicts?
Use light to get both energy and sync clock w/ light
- May conflict w/ each other bcuz twilight might favour clock for photosynthesis rather than clock for sunset/sunrise
Plant negative feedback loop
Cryptochrome (Crys)
Photosynthesis (Phys)
TOC1
Crys: Phase shifting and entrainment, measures length of day
Phys: Detects light
Negative feedback loop in middle w/ TOC1
How are growth and reproduction temporally separated (don’t happen at same time) from each other in plants?
Has loop connecting day and night genes (inhibitory)
- Day for reproduction (Glutamate release is inhibited in day)
- Night for growth
** Not the negative feedback loop (TTFL)
True or false;
when we sleep, closing our eyes even in the light causes SCN activity to increase
False
- Causes SCN activity to decrease bcuz we’re reducing its responsibility
- Less signalling via melanopsin from ipRCG
Acetabularia
nucleus removal experiment
transplantation experiment
nucleus entrainment
W/out nucleus in constant light, oxygen production rhythm persists
- Cytoplasm may be creating rhythm (and can be synced w/ light and dark)
Raised them in opposite light cycles
- Nucleus transplanted into each other shows og host’s rhythm
- Transplantation of stalk showed same result
Only illuminated nucleus
- Nucleus synced to light and drove rhythm of stalk
Conclusion:
- Clocks in both stalk/cytoplasm and nucleus
- Nucleus main pacemaker, which determines phase of cytoplasmic clock
- Example of distributed system (like sparrow)
Bulla gouldiana clock
Regulation of K channels
- Similar system as acetabularia
- Light causes depolarization of BRN and calcium entry
- Input sent to clock thru calmodulin CaMK to regulate K channel
- But in periodic light and dark, clock not needed as long as eyes can detect light
Cyanobacteria quinones
Changes in quinones on membrane detect oxidation and drive KaiC movement
- When reduced, allows KaiC to move to next phase
Cellular metabolism
W/out clock
Necessity
Red blood cell example
- Involved w/ circadian clock and reflects activity of cell
- Responsibility occurs even w/out circadian clock (can continue responding to light but lose ability to anticipate)
- Metabolic processes go up and down thruout day and in response to getting nutrients
- Clock useful for making it more precise but not necessarily if always getting food
Red blood cells rhythmic even w/out nucleus (clock)
- Continue to metabolize more at one part of day than others in 24-hour nutrient cycle
Peroxiredoxin cycle (PTO cycle of metabolism)
TTFL
CLOCK genes cause ROS expulsuon and ROS buildup
- Can exist independently from TTFL
- Can sync to external factors
- Affects ability to survive (know where things are, when to recover, etc)
Bmal1/Clock more involved in cardiometabolic control
Per/Cry more involved in nutritional status
3 oscillators important in metabolism
Transcriptional-translational oscillator
- Metabolism
Redox oscillator
Membrane excitability oscillation
- Important in bulla
- Also important for cells to communicate thru membrane
True or false
Cry/Per have different jobs other than interacting w/ Clock/Bmal1
True
- Together, they interact with them for clock output
- But also separately involved in different parts of gluconeogenesis, adipocyte differentiation (Per), inflammation (Cry)
Insulin feedback loop
Insulin detected by receptor
Activates mTORC1 to translate genes
Activates PER to create clock output for diff cell types
Creates behav output
Diffs in TORC1 (yeast) and mTORC1 (mammals) in metabolism
Yeast:
- Tunicamycin and rapamycin interact w/ TORC1
- Interacts w/ Sfp1 and Mpk1
- Mpk1 important in increasing RACs, proteasome subunits, proteasome levels, cell survival
Mammals:
- Nutrient starvation and Rapamycin interact w/ mTORC1
- Interacts w/ ERK5
- Increases same things as Mpk1
Feeding entrainment in suckling rabbit pups
Pups show daily feeding pattern
- Mother leaves after feeding and pups take this time to grow
- Mother has to leave so that pups aren’t always excited (makes them silent) so predator doesn’t hear them
Food entrainment in rats
Sporadic activity throughout night
- Burst of activity right before light turns on
Rats given food right before light turns off
- Shows anticipatory behaviour before night (getting ready to run)
- But rats continue eating thruout night anyway
- Excitement goes up before feeding and goes down when eating
Rat food entrainment w/ lever pressing
Rat gets less food over time
- Anticipatory behaviour persists but decreases in amplitude
- W/out food, anticipatory behav disappears
True or false
Circadian oscillator more entrainable than food oscillator
W/out SCN, anticipation can still appear when food is given at certain time
The SCN can be synchronized to food in rats
False
Food oscillator is more entrainable
True
True
True or false
Anticipation tends to disappear as T is lengthened or shortened
Lesioning SCN removes food anticipation and doesn’t continue when T is lengthened or shortened
True
False
Lesioning SCN still causes food anticipation and continues when T is lengthened or shortened
What happens to food anticipation when:
Cry1 is knocked out
Cry2 is knocked out
BMAL1 knocked out
Cry 1 knocked out
- Shorter tau
- Less anticipation on 21-h cycle
Cry2 knocked out
- Longer tau
- Less anticipation as cycles get shorter
BMAL1 knocked out
- Continues anticipation in all cycles
- Animal can learn T cycle
What is the SCN’s effect on the food entrainable oscillator?
SCN entrains or influences the phase of food entrainable oscillator only
Calorie-based food entrainment vs Chocolate (hedonic-based) entrainment in rats
Calorie-based:
- Short anticipation period
- When food given constantly, anticipation disappears (bcuz no need to run to look for food); Food anticipatory activity (FAA) less when no need for food
- When food taken away, anticipation returns
Chocolate (hedonic-based):
- Anticipation retains even when food given constantly (bcuz it’s more of reward than necessity)
Diffs between anticipation of food for its caloric vs hedonic value
- Caloric more hypothalamic regulation, hedonic more limbic control
- Both depend on circadian clocks outside of SCN
- Both influenced by SCN
- Both dopamine dependent
Methamphetamine (MASCO) / Dopamine (DARCO) entrainment thru scheduled feeding in rats
- W/out SCN
- W/ SCN
W/out SCN:
Rats given chronic methamphetamine in water
- Originally, activity at 30 hours
- Oscillation returns w/ restrictive feeding (food anticipation)
- When food is available thruout day, goes back to running at 30 hours
- Removal of methamphetamine causes arrhythmicity
W/ SCN:
- Methamphetamine given, causing lengthening of period
- Period temporarily gets shorter during time of day MASCO syncs w/ SCN
- When given nutella (attempt to resync w/ SNC), some activity appears but fails to successfully resync
Effect of mouse given food all the time + methamphetamine (MASCO)
Vs w/ daily food reward and MASCO
Food all the time:
- Bi-synchronization eventually occurs
(SCN only syncs with MASCO every other day)
Daily food reward:
- Food resyncs but in a bi-circadian pattern (every other day)
- Taking food away gets rid of anticipatory behaviour)
