Lecture 10 Flashcards
Limitations of the two factor model of sleep
Process S can only be measured while asleep.
Process C is not exactly a sine wave.
The history of hipnotoxin theory of sleep
French Physiologist: Henri Pieron 1913
CSF of dogs deprived of sleep for up to 10 days injected into the brains of well rested dog and induced sleep in the donor animals.
What is the proposed hypnotoxin
In 1995 Adenosine was postulated the factor behind process S.
Nucleoside that forms during breakdown of ATP
4 receptors in humans (A1, A2A, A2B, A3)
A1 and A2A: present in brain
Caffeine: antagonist at A2A
Relationship between adenosine and SWS
Coffee before bed inhibits sleep onset and reduce SWS amount.
Brain adenosine increases in an activity dependent fashion.
Injection of adenosine (or adenosine re-uptake blockers) induce SWS.
Evidence for adenosine being the hypnotoxin
In cats, adenosine levels in the basal forebrain rise during prolonged waking and fall during recovery sleep.
Adenosine is broken down by adenosine deaminase.
Genetic variability in adenosine deaminase results in slow or quick acting forms.
There is a strong correlation between reported sleep need, SWS amplitude and SWS amount and the form of adenosine deaminase that an individual has.
What could possibly be the mechanism behind sleep requirement difference
Adenosine is broken down by adenosine deaminase.
Genetic variability in adenosine deaminase results in slow or quick acting forms.
There is a strong correlation between reported sleep need, SWS amplitude and SWS amount and the form of adenosine deaminase that an individual has.
The evidence against adenosine being the hypnotoxin or not the sole factor behind process S
Microdialysis probe in human amygdalae (not a good place to use since it does not control sleep much) to measure adenosine during sleep deprivation and recovery - adenosine level in amygdala fell during wakefulness and rose during sleep. also depending on the brain regions level of adenosine either went up or down during wakefulness and all went down during recovery sleep (the first result was part of this latter larger study)
Adenosine receptors in brain regions where would be expected to increase wake.
Dynamics of build up and decay don’t match to process S (exponential function)
Extreme activity that increases adenosine should result in SWS increases but generally not observed.
Possible other process S factors
Cytokines:
proteins produced by leukocytes and other cells functioning as intracerebral mediators
interleukin, interferon alpha and tumour necrosis factor have all been shown to promote sleep.
Other sleep/immune factors
cholecystokinin, arginine vasotocin, vasoactive intestinal peptide, growth hormone-releasing hormone (GHRH), somatostatin, prostaglandin D
What is circadian rhythms and its 4 key properties and how to observe it
Self sustaining, daily oscillations
4 key properties:
Persist without time cues
Phase can be shifted by light/drugs
Period can be entrained (if near the intrinsic period)
Clock does not change with temperature
Can be observed in Core body temperature, Melatonin, Cortisol and lots of other variables.
How does circadian rhythm affect body temperature
body temperature drop during sleep
People were kept awake during sleep hours to have their circadian rhythms measure and what was the findings (they measured 6 things)
rectal temp drop from afternoon until midnight than gradually rise up again
cortisol drop hours before sleep then keep rising during sleep until peaks in the morning
grip strength drop doring night
dopamine is pretty chill, slightly drop during sleep
catecholamines drop fron afternoon and dpis during the night
optical reaction time fucking rise and peak during night time???!!!
What are suprachiasmatc nucleus and what they do?
Evidence?
The suprachiasmatic nucleus (SCN) contains a biological clock that governs circadian rhythms
it’s in the hypothalamus above the optic nerve
SCN lesions disrupt circadian rhythms
SCN cells do not require direct neural connections to control circadian rhythms, but may do using chemical signals
What are the behavioural outcome after lesion of SCN
random drinking behaivour regardless of day or night for the hamster
How do SCN cells know the time
Individual SCN cells exhibit circadian rhythms
The “clock” is set by proteins that inhibit their own production above a certain level.
In humans this is on average 24.3 hours, but is set to 24 hours by external signals
- 7-8 lowest level of per and tim activate clock, which triggers production of per and tim
- 11-12 levels of per and tim rise
- 15-16 - hiest levels of per and tim inhibit clock, resulting in decreased production of per and tim
- 19-21 - highest levels of per and tim - new production ceases
- 1-2 perand tim disintergrate levels start dropping
Factors influencing the biological clock
Melanopsin containing ganglion cells in the retina, a pathway that may account for the ability of light to reset the biological clock (zeitgeber function)
The intergeniculate leaflet of the lateral geniculate thalamic nucleus, a pathway for other environmental stimuli to set the biological clock (such as activity)
retinohypothalamic tract - suprachiasmatic nucleus - melatonin
food, activity - intergeniculate leaflet of the lateral geniculate thalamic nucleus - SCN
