Phase Response Curves Flashcards
1
Q
“Circadian” rhythm
A
- “Circadian” rhythm is so-called because it is “circa” about “dia” a day in length
○ Biological or circadian clock regulates the body
○ Aims to synchronise body to solar time, or external time
○ Now often overruled by social time, or clock time - Circadian rhythm is adaptable, entrains to the environment
○ Via light through the eyes, signal to suprachiasmatic nuclei (SCN) = subsequently sends that signal throughout the body
2
Q
Circadian rhythms as oscillations
A
- Rhythms can be described by:
○ Period: length of cycle
○ Amplitude: size of the peak
○ Phase: a particular point in the cycle
§ Acrophase: time of the peak
§ Nadir: time of the lowest point
○ Mesor: mean or average value
3
Q
Phase shift
A
- Refers to shifting the rhythm backwards or forwards in time
- Direction of change, phase advance or phase delay depends on when a zeitgeber/time cue is given
- Example:
○ Advance: earlier bedtime
○ Delay: later bedtime
4
Q
Circadian rhythm markers
A
- Activity of the brain clock cannot be directly measured in humans
- Circadian rhythm measured by:
○ Melatonin rhythm = how much melatonin there is in the bloodstream
○ Core body temp rhythm - Reference for circadian phase
○ Dim light melatonin onset (DLMO) = point at which melatonin starts to rise in the evening = usually occurs 2-3hrs before bedtime
○ Core body temp min (CBTmin) = usually occurs at about 4:00am
5
Q
Zeitgebers
A
- Light is the primary time cue or zeitgeber in humans
- Exercise also appears to be a zeitgeber
- Exogenous melatonin is a chronobiotic i.e. a substance that can entrain circadian rhythm
- Food intake may be a zeitgeber to peripheral clocks
* Needed for entrainment to solar time because innate free-running period of brain clock not exactly 24 hours
○ ~75% longer than 24 hrs; easier to delay
○ ~25% shorter than 24 hrs; easier to advance
○ Associated w/ chronotypes
6
Q
Phase response curve for light: timing
A
- Circadian response to light described by phase response curve
- Direction of phase shift depends on the time light is given
- Size of shift depends on:
○ Timing of light
○ Brightness (intensity) of light
○ Colour (wavelength) of light
○ Duration of light
7
Q
PRC for light: brightness/intensity
A
- Brighter (more intense) light produces a larger phase shift
○ Room light is ~100-300 lux
○ Sunlight is ~1,000-100,000 lux
○ Lux is unit for light intensity - When core body temp is at 0, there is this sharp shift in what happens to the circadian rhythm in response to light
- Before CBTmin = have an enormous phase delay = if get bright light in the early hours of the morning e.g. 2-4:00am, if get light in the early hours of morning around dawn = phase advance the rhythm
- People who are highly sensitive to light = they experience a greater suppression of their melatonin levels at lower levels of light e.g. at 10 lux, melatonin levels already suppressed by about 50%
- Whereas people who are less sensitive to light = have to get to artificial room lighting levels or b/w 100-1000 lux to achieve the same sort of suppression of their melatonin rhythms
- Lots of variation b/w people
8
Q
PRC for light: wavelength/colour
A
- Blue light produces a larger shift in circadian rhythm
○ Melanopsin cells in eye most sensitive to wavelengths ~440- 480nm
○ Our visual system is more sensitive to this rainbow band whereas our circadian response is much more sensitive to blue colour lights
§ Means when we are exposed to blue light around ~440- 480nm = the circadian system responds in a stronger way - Strongest in that blue light area = mean electronic screens do have a big impact on our circadian rhythms as we do tend to hold them close to our eyes + tend to use at night
- Common sleep advice: avoid electronic screens in evening, esp. in hrs before sleep to avoid delay of sleep onset
9
Q
Size of phase shifts
A
- In the lab, can achieve large phase shifts
○ Accurate measures of circadian phase
○ History of light exposure is minimised
○ Other zeitgebers + potential zeitgebers are controlled e.g. sleep = is a time cue - In practice, can achieve ~1 hr phase shift each day
○ Difficult to assess circadian phase exactly
○ History of light exposure
○ Example of jetlag: need ~1 hr to adapt for every time zone crossed- Aided by mathematical modeling of circadian rhythms
10
Q
Application of PRC for light: jetlag (1)
A
You are flying from Sydney (UTC +11) to Perth (UTC +8).
* a) How long would it take to adapt to local time in Perth?
○ Need about 1 hr to adapt for every time zone crossed
○ Difference b/w Perth + Sydney time i.e. +8 - +11 = -3 hours
○ Need about 3 days to adapt to Perth time
- b) Does this require a phase advance or a phase delay?
○ Sign of the difference tells us whether it is an advance (+) or delay (-).
○ Here need to delay 3 hrs (Perth is 3 hrs behind Sydney). - Generally when we fly in a westerly direction = need to phase delay, in an easterly direction = phase advance
11
Q
Application of PRC for light: jetlag (2)
A
- c) When should you get light + avoid light to minimise jetlag?
○ Need to delay 3 hrs to adapt to time in Perth
○ Best ways to delay according to PRC for light are to:
§ avoid light in the mornings right after you wake up (avoid phase advance)
§ use light in the evenings (facilitate phase delay)
○ Jetlag is an example where the env is helping you to adapt i.e. sunlight, hours of activity/ wakefulness
○ Note: calculation using time zones may not work where the time zones do not correspond approximately to sun time (e.g. China one big time zone). Instead, use degrees of longitude where 15 degrees ~ 1 hr difference in solar time
12
Q
Application of PRC for light: jetlag (3)
A
You are flying from Sydney (UTC +11) to Hawaii (UTC -10).
* a) How long would it take to adapt to local time in Hawaii?
○ Need about 1 hr to adapt for every time zone crossed
○ Difference b/w Hawaiian + Sydney time i.e. (-10) – (+11) = -21 hrs
○ Need to phase delay 21 hrs because time in Hawaii is behind Sydney
○ Or, only need to phase advance 3 hrs!
- b) How best to achieve the phase shift?
○ Get light in the morning (Sydney time)
○ Avoid light in the evening (Sydney time)
○ Reference point is always biological clock, which is approximated by time at origin if entrained = because the phase response curves are worked out based on the circadian clock time not the times for example in hawaii
13
Q
Exercise as a zeitgeber
A
- Recent discovery in humans 1990+, previous described in rodents
- Phase response curve for 1 hr of treadmill walking, moderate intensity (Youngstedt 2019 J Physiol)
- Similar effects to light: advance in morning (+) + delay in evening (-)
○ Possible region of advance in afternoon - Similar effect size to light: ~1 hr
14
Q
Exogenous melatonin as a zeitgeber
A
- Melatonin supplements can be used as a chronobiotic
- Used as a short-term sleep aid
- Effective for people w/ difficulties falling asleep or travellers for jetlag (0.5– 5mg, within 2h before bedtime)
15
Q
Exogenous melatonin
A
- PRC for melatonin about 12 hrs out of phase w/ PRC for light
○ E.g. melatonin brings forward sleep in those w/ delayed sleep phase disorder (~70 min)
○ So if take melatonin in the evenings before/around DLMO = going to advance circadian rhythm = also what helps to advance your sleep + help you fall asleep quicker
○ Whereas if take melatonin around CBTmin or afterwards = delay the rhythm = shift bedtime later - In Australia, prescription only
○ Interaction w/ other meds
○ Unclear safety in children - Adverse effects in epilepsy + pregnancy
