W5L2 - Homeostatic and Circadian regulation of sleep Flashcards
1.) Discuss the homeostatic regulation of sleep. Adenosine Inflammatory cytokines 2.) Explain the basis of Circadian rhythms biologically. Suprachiasmatic nucleus 3.) Describe the evidence for and against the idea that Process S and C are independent.
What are some things to note for the Process S and C model
Process S
- Can only be measured while asleep because process S is reflected in slow wave activity
- Initial theory was speculative
- During naps, SWS was proportional to time awake (Later nap = More SWS)
Process C
- Not exactly sine wave
- Regular or Smooth
- Circardian dip around 1-3pm
What is the experiment behind hypnotoxin theory of sleep
- Hypotoxin (sleep toxin) builds up when awake and increase need for sleep
- Dogs: Deprived of Sleep by harness
- CSF of dogs deprived of sleep (up to 10 days) were injected into brains of well-rested dogs
- Induced sleep in the donor animals
- Hypotoxin that builds up to induce sleep
- Dogs: Deprived of Sleep by harness
What is the key mechanism behind process S. What is the NT and what are the receptors
Adenosine
- Nucleoside that forms from ATP breakdown
- 4 Receptors: A1 ; A2A ; A2B; A3
- A1 ; A2A : Brain
- A2A : Caffeine antagonist
3 Evidence for Adenosine behind Process S
- Coffee before bed inhibits (a) Sleep Onset; (b) Reduce SWS amount
- Brain adenosine increases in an activity-dependent fashion
- Injection of adenosine/ Adenosine re-uptake blocker induce SWS
What is the animal evidence for adenosine behind process S
In cats, adenosine levels in basal forebrain rise during prolonged waking and fall during recovery sleep
Further evidence for adenosine behind process S: Individual Sleep Requirement
- Adenosine is broken down by an enzyme called adenosine deaminase.
- Large genetic variability in adenosine deaminase (resulting in slow/quick acting form)
- Strong correlation between reported sleep need, SWS amplitude and SWS amount and the form of adenosine deaminase (short or long) that an individual has.
- Need more sleep = Long acting form of adenosine deaminase = More time to break down adenosine in the body
Zeitzer Sleep (2006): Methods and Results
Zeitzer Sleep (2006): opposing view of adenosine contributing to Process S
- Microdiaysis probe in amygdala, measuring adenosine during sleep deprivation and recovery in epileptic patients
Results
- Baseline sleep period
- Adenosine decreases as expected
- Wakefulness
- Adenosine decreases over time
- Under homeostatic theory, adenosine should increase gradually over sleep deprivation period
Further evidence for adenosine not being sole factor for process S
- There are vast adenosine receptors in brain regions responsible for wakefulness
- Dynamics of adenosine build up and decay (Linear) don’t match to process S (Exponential)
- Extreme activity that increases adenosine should result in SWS increase but it is generally not observed
- e.g. marathoners
What are the criticisms of Zeitzer Sleep (2006) study
- Generalisability: Epileptic patients
- Microdialysis probe might block adenosine from getting in but in the recovery period, there was a rise in adenosine (so this probably isn’t a limitation)
- Only on the amygdala (Basal forebrain, other areas might increase)
What are other process S factors
- Cytokines
- Protein produced by leukocytes and other cell functioning
- Shown to promote sleep
- Other Sleep/Immune Factors
- Cholecyostkin, etc
What are circadian rhythms. What are the 4 key properties. When is it observed
Circadian Rhythms
- Self-sustaining, daily oscillations approximately 24 - 24.5 hours
Properties
- Persist without time cue (Plants)
- Phase can be shifted by lights/drugs
- Period can be entrained (if near intrinsic period)
- Clock does not change with temperature
Observed in any bodily function/system – in sleep we commonly look at circadian rhythms in respect to core body temperature, Melatonin, Cortisol and lots of other variables (e.g. heart rate, breathing, blood pressure)
What is the circadian rhythm in other body systems
- Body temperature
- Fluctuation is constant despite manipulating light
- Rectal temperature
- Sine wave looking function (increases during daytime hours and decreases during night)
- Cortisol levels
- Linear decrease during the day, where it reaches its lowest levels at night and rises back up again
- Dopamine, etc…
What is Suprachiasmatic Nucleus (SCN). What happens in lesion? And how does it signal
- SCN contains a biological clock that governs circadian rhythms
- Lesion disrupt circadian rhythm (Animal Study)
- SCN cells do not require direct neural connections to control circadian rhythm (Use chemical signal)
- Implanted SCN into a lesioned animals, animal can restore circadian rhythm
What is the behaviour after lesion of SCN in hamsters?
Before SCN-lesion
- Most of time drinking at night
After SCN-lesion
- Drinking behavior no longer restricted to nighttime
- But if you implant an SCN from a healthy animal, the circadian rhythm will recover and the pattern will revert
How do SCN cells know the time?
- Individual SCN cells exhibit circadian rhythms
- In humans this is on average 24.3 hours, but is set to 24 hours by external signals
- Set by proteins that inhibit their own production above a certain level
- Low level (Morn) > Transcription > High > Cease production (~8pm) > Drops till morning
What are the 2 SCN inputs (How cells get information about daylight)
SCN Inputs: Light & Activity
- Some Ganglion cells in retina contains Melanospin (Light-sensitive protein;zeitgeber function)
- Send a signal via the retinohypothalamic tract to the SCN to relay light information
- Intergeniculate leaflet of the lateral geniculate thalamic nucleus/LGN (Pathway for other environmental stimuli)
- Information about activities
- E.g., in blinds, normal circadian rhythm through this pathway by using regular activities to set this rhythm (e.g. bathing at the same time every night)
