BBS2051 Summary
By Grace Marshall and Nile Verleur
Case 1- Circadian Rhythms
PS: how does the biological clock influence processes in the human body?
Learning Goals:
- What is the biological clock
- Where are they located
- How do they communicate?
- What are the molecular mechanisms of the clocks?
- Per genes
- DBT
- TIM
- What factors influence the clock?
- Light (main focus)
- Others
- Nutrition
- Time of meals
- Quality of meals
- Exercise
- What does the clock regulate?
- Hormones
- Digestion
- Body temp
- Sleep
- Metabolism
- Does living in a natural environment improve the function of the biological clock? Is this why Jan
was more awake in the morning?
Circadian Rhythm
A circadian rhythm is “any biological process that displays an endogenous, entrainable oscillation of
about 24 hours.” This rhythm is driven by a circadian clock. It’s one of the things that is spread
throughout the natural world- plants, animals, fungi, and bacteria have all be observed to have an
innate clock feature.
,There’s a few things we take as standard:
- circadian rhythms are ubiquitous in living systems (every living thing has them);
- they are innate (even those animals that never meet their parents will sleep);
- they are not learned from the environment (you don’t watch something else fall asleep and go
“wow what a great idea”);
- they occur autonomously at both cellular and whole-organism levels of organization;
These observations lead us to what is now definitely known to be the case: A cell-autonomous program
of gene expression makes up the mammalian circadian “clock” that produces these rhythms.
In simple terms, it is our daily rhythm of sleeping for 8 hours and being awake for 16.
The rhythm alternates on zeitgebers - “time keepers”- including obvious stuff like day and night and less
obvious stuff like the earth’s magnetic core. However, even without these external time keepers, we
would naturally fall into a daily rhythm.
An extra titbit for all you conspiracy theorists out there, a human’s natural endogenous cycle is 25 hours
and not 24. Things that fuck up this cycle include jet lag, drugs and binging netflix until 2am when you
have an 8:30 tutorial.
So, if you have a daily cycle then you need a clock to keep track.
In mammals like us, this clock is controlled by a region of the brain called the hypothalamus (hopefully
you remember it), which is the master centre for integrating rhythmic information and establishing
sleep patterns. Within the hypothalamus is the suprachiasmatic nucleus (SCN) which is the location of
the central clock.
It’s called the suprachiasmatic nucleus because it sits above (“supra”) the optic chiasm (“chiasmatic”).
,The SCN is the master central clock, coordinating all other clocks. It consists of neuronal and glial cells
in two anatomic subdivisions: a ventral “core” region, receiving retinal input, and a dorsal “shell” region,
receiving dense input from the core. Most synapses between SCN neurons are GABAergic. The majority
of core neurons express vasoactive intestinal polypeptide (VIP), and fewer express gastrin-releasing
peptide. #VIP acts through the elevation of cAMP levels in the SCN. In contrast, most shell neurons
express vasopressin.
It works to regulate behavioural and physiological rhythms, synchronising them to occur in the proper
timing with respect to the light-dark cycle. Light is detected by rods, cones, and a special population of
intrinsically photosensitive retinal ganglion cells. The luminance information (how light it is outside) is
relayed to the SCN, where it influences the phase of molecular oscillations.
You can take a SCN out of the brain and culture it in a little petri dish and it will still generate circadian
rhythms of electrical activity. By looking at the firing rate of dissociated SCN neurons, single-cell
circadian pacemakers were found, which express circadian oscillations with different phases and
periods. SCN neurons are intrinsic but unstable oscillators, which need network interactions to stabilise
, them. The SCN as a whole is much more stable and accurate than just one SCN neuron. SCN-neurons
coordinate their oscillations through neurochemicals, most notably vasoactive intestinal peptide (VIP).
The Molecular Clock
The molecular clock machinery involves 24-hour oscillations of core clock components called clock genes
(genes whose protein products are necessary for generating circadian rhythmicity within individual
cells).
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