Wk 2: Sleep and Circadian Rhythms

The physiological system responsible for measuring time and synchronising an organism/s internal processes with the daily events it its environment

• Circadian: day
• Circa: approximate Die: day
• Circannual: year eg. migration of birds
• Some circannual rhythms are actually circadian rhythms
• circalunar: moon
• circatidal:
• Ultradian rhythms: rhythms that occur many times a day eg. sleep cycles
• Infradian rhythms: longer than a day (eg. menstrual cycle)

• Virtually all organisms have circadian rhythms
• Ancient:
• Organisation of internal physiology to operate on 24 hour cycle
• -Body does not expect to digest food middle of the night. This is why shift workers have gastro intestinal problems
• Anticipation of important events: eg. better to get photosynthetic tools ready just before light is on
• Predicting environmental events
• Anticipating risks
• Predicting when food is available. Eg. flower opens up at certain times of the day so bees only go out during that time
• -Good for plants manipulating bees to maybe not be available during time where many other plants are available creating a temporal niche, hunting

• Modern:
• Orientation
• Seasonality (eg. mating)
• Optimise an organism's physiology and behaviour to best meet the varying demands of the day/night cycle

• Endogenous: From within the organism
• Endogenous pacemakers: Internal body clocks
• Exogenous zeitgeibers: external stimuli that affect the body clock.

• Mimosa pudica plant (aka sensitive plant)
• Open during the day and close at night
• De Mairan 1726
• Demonstrated that the leaf movements were not a passive response to light, but likely endogenous (coming from within).
• When plants were placed away from light/dark, still opened during the day and closed at night.

• Endogenous: coming from within
• "Free running": period close to but does not equal the cycle that is being measured. When internal clock runs without external zeitgeiber
• Settable (synchronisable, entrainable) to cyclic environment
• Innate (genetically coded)
• Period compensated for temperature changes (if it's a cold day, doesn't run slow. If it's a hot day, doesn't run fast)

• Women tend to be morning type (less than 24) and men tend to be evening type (longer than 24hr cycle)
• But we all generally keep 24hr clock because it is synched/entrained by light and other factors.
• Why not have perfect clock? In order to have a stable relationship between internal clock and 24hr time, internal clock needs to be a bit off so it can be reset.

• Phase: Can think of this as time of day. Representation of a state as a point on a circle where the circle represents one complete cycle.
• Eg. 6pm is a phase
• Phase shift (ΔΦ): A change in time. A rapid change in an oscillation from one phase to another 
• Eg. If body clock thinks it's midnight, we can phase shift it to think it's 10pm by changing light.

• Phase angle difference (Ψ): also called phase angle of entrainment. The difference between some internal time and external time. The difference in degrees (or hours) between reference points on two oscillations.
• Eg. difference between timing of melatonin onset rises naturally 2hrs before bed (that is a phase driven by internal clock) and time of sleep, which is usually 2 hours later.
• Important because this is a description of how your body aligns to your environment.

• tau: length of endogenous rhythm (DD/LL). Also known as the “period” of the rhythm. Eg. 24.5hrs is your tau
• Zeitgeber: time giver. Something that changes your internal clock time. (usually a light cycle).
• The period/length of zeitgeber represented as T.
• Zeitgebers cause phase shifts.
• Subjective day/night:
• correspond to day/night while on a light cycle. Used to determine phase of cycle while in constant conditions (when the animal thinks its day/night internally when all external cues are taken away.)
• Eg. an animal that runs at night starts running without external cues, that would be its subjective night.

• Circadian time (CT): refers to the organism’s “inner” day. One CT used as a reference point.
• Eg. CT0 might be start of day and Circadian time 12 is night.
• If hamster starts running, that might be 12CT
• Zeitgeber time (ZT): refers to the “outer” day. One ZT used as a reference point
• Eg. zeitgeber time 0 will be when lights go on, zeitgeber 12, when lights go off

• Actogram
• Top is its internal clock when it is entrained by light. 12hrs light, 12hrs dark.

• Second graph is its internal clock without light (free running).
• Goes later every day meaning it is longer than 24hrs.
• In this case, tau= 24.1

• LD= light-dark cycle
• DD: constant darkness
• Tau †: free running period
• Mice run a little bit earlier each

23.5

25 hours

• Internal clock of the blind
• 
• Most melatonin is where the red spots are
• The lines are when the person is asleep
• Can see that when melatonin is high during the day, person tends to take more naps.
• Perpetual jetlag.

• Two ways that entrainment can occur
• 1. Change the period
• 2. Reset the phase

• You can change the internal clock's free running rhythm (tau) through entrainment.
• These changes are called "after-effects"
• 
• Tau was originally 24 during DD.
• After LD entrainment of 24 hours, tau during DD changed to 24.3 (shorter).

• ^two mice with similar taus. First one is entrained gradually to 20hr cycle, the second to 28hrs.
• Found that once in DD, 1st mouse tau=23.5. 2nd mouse tau=24.5
• Evidence of after-effects

Older people have taus closer to 24hr compared to younger people, part of that is probably after-effects

• endogenous 'circadian' clock does not equal 24h even while entrained
• Therefore the clock must be reset every day.

The same light may produce delays (slowing down internal clock) or advances (speeding up internal clock) of appropriate size, depending on when in the cycle the light falls.

• Black lines are sleeping time.
• Phase delay: when exposed to light in evening or early night
• Eg. using a phone at night
• Phase advance: offset occurs when exposed to morning light

Phase shift of 3hrs

Phase shift of -3 circadian hrs

• The relationship between two synchronised oscillators is:
• 
• Where ΔΦ represents the net effect of delays and advances.
• Tau- (usually 24hrs)= phase shift needed
• Delays are negative
• Advance are positive
• Entrainment is accomplished primarily through daily phase delays and advances of the endogenous circadian rhythm.
• In addition, the pattern of the Zeitgeber cycle influences the underlying period (tau).

• Response to light depends on time of day or phase in the cycle
• 

• 
• Yellow: subjective day
• Purple: early subjective night. If exposed to light during this time, causes a phase delay, where your tau is pushed back. Meaning it thinks it's earlier than it is.
• Light blue: late subjective night. When exposed to light during this time, causes a phase advance, where the tau is pushed forward. It thinks it is later in.

• A: light pulse middle of the day- has no change in phase
• B: small phase delay
• C: Big phase delay the next day
• D: give light pulse earlier than normal, causes light phase advance the next day
• E: phase advance

• 
• If you make mistake in forbidden zone it is amplified and would be unstable.
• Hitting the singularity: hitting light pulse in forbidden zone over time causes all internal clocks to go out of rhythm.

• is the expression of circadian rhythmicity that is subject to natural selection.
• For photic entrainment, the period (τ) and the PRC are characteristics of the system that determine y.

• In nature, ψ may be altered by:
• Changing the circadian period (In the laboratory, ψ may be altered also by changing the Zeitgeber period)
• Changing the sensitivity of the system to the Zeitgeber (PRC amplitude).

• Men= ave 24h 11m
• Women= 24h 5m
• Equals to about half hour difference in timing
• Melatonin onset for women is half hour earlier
• Core body temp min occurs earlier (strongest single for sleep), which means women have less signal for sleep in latter half

• Entrained rhythms are fragmented if tau does not closely match Zeitgeber cycle.
• Affects life cycle
• Sleep and active at different times of day (fragmented)
• Study showed that longevity is determined by matching up of internal and external rhythm.

• 
• Red line has lower responsiveness to light
• If they have the same period (23.5 hrs) where does dusk have to fall for them to synchronise?
• I think pretend the flat line at start is 0 and the thin line is the phase shift needed (a phase delay)
• The vertical lines are internal dusks (subjective early night) for each animal
• We have to match up dusks- to do that, red needs to go to sleep and wake up half an hour earlier (phase advance)
• This means has to be exposed to light half an hour earlier (wake up half an hour earlier)
• 

• For a phase delay of half an hour for black, wake up at dusk
• For the same phase shift (30min) for red, must be up

• The expression of the underlying rhythm shows up in the environment as phase angle and that is naturally selected.
• In humans, can  determine the quality of sleep and secondary health outcomes, like weight, cardiovascular health, mood and even vulnerability to cancer.

• 
• Red dots are ideal min core body temp
• Bars are sleep time

• Insomnia: core body min very far away from ideal
• eg. first one has trouble maintaining sleep
• Second one has strong signal to stay awake at night and strong sleep in the morning.

• Light is a universal phase shifting/entraining stimulus
• Other stimuli can also induce shifts in circadian timing
• These shifts are called non-photic

Dark pulse in constant light cause phase shifts in the subjective day

• 
• Novel running wheel access has the same effect.
• Common feature appears to be arousal during the day for nocturnal animals.
• Trying to wake up the next day earlier to be there when the arousal is available.

• Edwin Bunning
• Raised 30 generation of fruit flies in constant light to eliminate rhythms.
• Dropping the flies into constant dark from constant light produced 24h rhythms.
• Demonstrated that exposure to 24hr rhythms unnecessary for rhythm generation.

Never experienced 24hr rhythms, but one stimulus that told them it was dusk and they made they own rhythm.

• Colin Pittendrigh
• Showed that flies have a clock that is temperature compensated
• Period compensated for temperature changes  (Q101)
• The Q10 is the ratio of the rates of a process at a 10 degree difference in temperature.
• A Q10 of 3 means that the process goes 3x as fast at 37 degrees than at 27 degrees.

• Orientation
• Bee will go out and find food source, come back to the hive and perform dance
• The angle at which it dances and the intensity at which it waggles (how far)
• Uses the sun as a compass
• 
• Because the sun moves, later on the same bee can do the dance but at 70 degrees to compensate for the sun moving.

• 
• Chrys: short day plant. Takes short time to flower during short days and takes longer to flower in long days. Wants to flower during winter, using day length to know.
• Henbane: flowers a lot in long days

Measures in some ways how much light in a 24hr period.

Tested whether it counts how many hours of light there is OR when the light occurs



They have 24hr rhythms and all they need is some light to signal that it is long/short day.