Chronobiology of sleep Flashcards
Homeostatic drive for sleep:
1- why does sleep tendency increase?
2- what happens if the time we are awake increases?
3- what happens if sleep is delayed?
4- what accounts for the homeostatic drive for sleep?
1- due to being awake a long time
2- the length of time we are awake increases, sleep pressure mounts and we accumulate sleep debt
3- If we delay sleep and stay awake for longer than usual, we will sleep for a longer period once we get the chance to sleep, known as sleep rebound
4- adenosine build up
Circadian pressure for sleep:
- what is another factor affecting our tendency to go to sleep or be awake?
- according to Borbély (1982) what two processes is sleep controlled by?
- what is this known as?
- Also, the time of day (light and darkness) affects our tendency to go to sleep or to be awake
- Borbély, 1982: Sleep is controlled mainly by two processes:
— Homeostatic (S) and Circadian (C) pressures govern a predictable pattern of maximum sleepiness and maximum alertness throughout the 24h cycle
— This is widely known as the two-process model for sleep
Two-process model of sleep (Borbély, AA)
S drive is telling us we’ve been awake for a long time and we should go to sleep. Then this becomes quiet until the next time we wake up.
The C is regular- daytime and nighttime
Biological rhythms
1- what are endogenous cycles?
2- how have endogenous rhythms evolved?
3- Circadian “circa” and “diem” meaning
4- what is the most prominent circadian rhythm?
1- Endogenous cycles (“generated from within”): Living organisms display regularity in certain behaviours, that are generated within the organism. They match light and dark cycles.
2- Endogenous rhythms have evolved through evolution on planet earth and can be of various durations, ultradian or seasonal (breeding, hibernating, migrating, etc)
- offers the advantage to plan ahead i.e store food
3- Circadian “circa” and “diem” - rhythms or regular patterns of activity associated with a 24h-cycle associated with the earth’s rotation
4- The most prominent circadian rhythm is that of sleep and wakefulness but there are many more
Average Body Temperature
This also has a circadian rhythms
Body temp fluctuates based on the 24 hour circle
When we go to sleep its 0 and then after 2/3 hours after we go to sleep out body temperature takes a dive. Then before we wake up it starts to climb.
Circadian Rhythms across functions
- melatonin- starts to get secreted in the evening and then it goes down the next day
- temperature
- alertness- drops in the evening
- task performance- gets bad in the evening / early morning hours
- triacyglycerol
Early discoveries:
- what are biorhythms not unique to?
- 1729 what was discovered?
- Biorhythms are not unique to humans and animals
— Plants and flowers may open during the day and close during the night - 1729: French geologist, Jean Jacque d’Ortous de Mairan experimented with the mimosa plant
— Even if isolated from light, dark or temperature cues the leaves continued their rhythmic behavior
Suspecting its Existence: Curt Paul Richter, Prof. of Psychobiology at Johns Hopkins (1927)
1- what concept did he introduce?
2- what did he perform?
3- what happened to rats?
4- book name and hypothesis?
1- Introduced the concept that the brain generates its own rhythms, so it must have a biological clock which he attempted to locate in the brain of wild rats
2- He performed electrical lesions in various parts of their brain in order to locate the biological clock
3- The rats lost their rhythmic behaviour after damage to the hypothalamus (he thought if this rhythmicity is lost it will cause probelms with the biological clock and be detrimental to our health)
4- In his book “Biological clocks in Medicine and Psychiatry” (1965) he hypothesized that many disorders may result from disruption of the biological clock
What is the biological clock? (disruptions causing)
(R.Y. Moore & V.B. Eichler (U Chicago) and F.K. Stephan & I. Zucker (UC Berkeley), 1972)
The suprachiasmatic nucleus (SCN) of the hypothalamus
Lesions of this nucleus disrupted circadian rhythms of wheel running, drinking, and hormonal secretion – thus named the “master clock”
The suprachiasmatic nucleus (SCN):
1- what does it consist and location?
2- what does it generate?
3- lesion implications?
1- The SCN consists of a group of cells in the hypothalamus, right above the optic chiasm (“supra” and “chiasm”)
2- The SCN generates circadian rhythms in a genetically controlled manner – even if raised in constant light or dark conditions the animals develop circadian rhythms
3- If the SCN is lesioned the animals still engage in behaviors but in a haphazard way
The SCN:
1- activity of neurons? (time of day)
2- function?
3- impact of transplantation of SCN?
1- Recording electrodes in the SCN confirm that neurons are more active during the light period than during the dark period
2- Autonomous function - a single cell extracted from the SCN and raised in tissue culture continues to function in a rhythmic pattern
3- Transplantation of an SCN into a donor organism results in the recipient following the donor’s rhythm (the donor will dictate the activity of the recipient)
SCN firing in light vs dark
(Pattron and Hastings, 2018)
firing only during day time and then quiet during night- showing a clear distinction of when its day and night. (this persists so if you put them in a dish they will continue to do this- the clock is still ticking)
lights on - they stop exercising. When the lights are off they start exercising.
The experimenters then kept it dark- the mice had an idea of when the lights used to be on so they maintained their rhythmicity.
What makes this clock tick?
Findings of…
- Konopka and Benzer 1971
- Jeffrey Hall & Michael Rosbash
- Michael Young
Konopka and Benzer 1971: the 24h cycle was changed in mutant flies
- (Drosophila Melanogaster) and suggested a gene on the X chromosome
- Then the 3 researchers below discovered one by one the genes and it took some time to discover how these come together to create the function of the clock.
Jeffrey Hall & Michael Rosbash
- Studied the SCN in Drosophila
- 1984: Discovered the “per” gene and the “PER” protein (period)
— The PER protein builds up and goes down within a 24-hour cycle
Michael Young
- 1994: Discovered the gene “tim” that produces the “TIM” protein (timeless)
- When TIM meets PER they combine and shut the period gene down
What about in mammals?
1- what did work from fruit flies show?
2- what was found by chance?
3- What did Joseph Takahashi at Northwestern University do?
1- Work from fruit flies to mammals showed that the system is conserved across species
2- Mutant golden hamster found by chance, to have a rather short period of ~20-22h long – (Ralph and Menaker, 1988, Science)
3- Joseph Takahashi at Northwestern University actively searched for mutations in circadian rhythms in mice (forward genetics- trying cosmetations and then looking at changes in behvaiour)
— Identified a mutant mouse with particularly long cycle of ~25-28h (Vitaterna et al., 1994; Takahashi, Pinto and Vitaterna, 1994)
— The mutation was in the clock gene
The Molecular Mechanism:
In Drosophilla vs Mammals
Drosophilla:
2 proteins that act as transcription factors. They come together into the enhancer box and they initiate the transcription of certain genes (per, tim). They start to be transcribed and translated into the per protein and tim protein. These are in the cytoplasm. They start to accumulate and as they become more and more they start to bump into each other and become dimers. They both walk together now. When they are dimerised they go back into the nucleus and acts as repressors. They act to inhibit the transcription that really produced them in the first place. Inhibit until there is few of them left and the production is stopped. Takes place in 24h time period.
Mammals:
- Similar situation
- Changes in proteins
- The activators are the clock and the BMAL 1. These initiate the transcription of the Per 1-3 or Cry1,2. These translate into proteins in a similar way, they dimerise, come back into the nucleus and inhibit their own production.
Transcription-Translation-Inhibition- Feedback loop
1- what are involved in this clock
2- what process
3- what happens next
4- what happens again
1- A few genes and their protein products are involved in this clock
2- Transcription from DNA to mRNA, to translation into proteins which form dimers
3- These dimers enter the nucleus in order to inhibit transcription and then they decay
4- The cycle begins again in a daily rhythm
(When we are awake there is the mRNA that is rising for the per and time as they get transcribed and translated. Then they go down at night time. The opposite as true because the proteins take time to form but when they form they inhibit production and also decrease. )