Circadian rhythm

Sleep mechanism and sleep-wake cycle

Every night we retire to our bedroom, climb into bed, and drift off into the unconscious state of sleep. Most of us sleep for about 8 hours, which means we spend roughly a third of our lives unconscious – part of it dreaming.  If you try to avoid sleep to use this precious time for other activities, such as late night parties or burning the midnight oil cramming for exams, your body and brain will soon tell you that you shouldn’t.  We can stave it off for a while but never for long.  The sleep/wake cycle is one of a number of rhythmical activities of the body and brain.  Why do they exist, what parts of the brain are involved and how do they work?  

The sleep-wake cycle

The sleep-wake cycle is an endogenous rhythm that gradually becomes locked to the day-night cycle through the first years of life.  It is what is called a circadian rhythm so called because ‘circa’ is Latin for around, and ‘dies’ for day. It is important throughout life: babies sleep for short periods during both the day and the night, young children often take a nap after lunch, while adults generally sleep only at night. Sleep is good for you – Winston Churchill, the Prime Minister during World War II, was said to be partial to short naps of five minutes or so – sometimes during cabinet meetings!

Circadian rhythm and daily activities: daily routine of a woman and sleep-wake cycle, healthy lifestyle concept

The normal pattern locking in sleep and wakefulness to the day-night cycle is partly controlled by a small group of cells in the hypothalamus just above the optic chiasm called the suprachiasmatic nucleus.  The neurons here, which are unusual in having lots of synapses between their dendrites to synchronise their firing together, are part of the brain’s biological clock. 

In humans, it ticks away at a rate just a bit slower than a day, but is normally kept in register by inputs from the eye telling it when it is day-time or night-time. We know this because people who have participated in sleep experiments by living in deep caves for long periods of time, away from all clues as to the true time of day, adopt patterns of activity that free-run to a sleep waking cycle of about 25 hours.

The stages of sleep

Sleep is not quite the passive process it seems. If a person is wired up with electrodes to their scalp in a sleep laboratory (which has beds not benches!), the brain’s electroencephalogram (EEG) passes through several discrete stages. When awake, our brains show low-amplitude electrical activity. As we fall asleep, the EEG becomes flatter at first but then, gradually, it shows increases in amplitude and decreases in frequency as we move through a series of discrete stages of sleep.

These stages are called slow-wave sleep (SWS).  The reasons for these changes in electrical activity are still not fully understood.  However, it is believed that as neurons in the brain become unresponsive to their normal inputs, they gradually become synchronised with each other.  You lose muscle tone as the neurons controlling skeletal muscle movements are actively inhibited but, thankfully, the ones controlling respiration and heart rate carry on working normally!

Throughout the night, we cycle back and forth between these different stages of sleep. In one of them, the EEG becomes like the waking state again and our eyes jerk back and forth beneath our closed eyelids. This is the so-called rapid eye movement (REM) stage of sleep when we are more likely to dream.  If people are woken during REM sleep, they almost invariably report dreaming – even those who habitually claim that they never dream (try it as an experiment on a member of your family!).  In fact, most of us will have about 4 to 6 short episodes of REM sleep each night. Babies have a bit more REM sleep and even animals show REM sleep.

Sleep Deprivation

Some years ago, an American teenager called Randy Gardner resolved to try and win his place in the Guinness book of Records by going without sleep for the longest period ever recorded. His ambition was to last 264 hours without sleep and he did it!  It was a carefully controlled experiment supervised by doctors in the American Navy – not one we recommend you repeat!  Amazingly, he survived very well.

The main difficulties he had (apart from feeling very sleepy) were difficulties with speech, an inability to concentrate, lapses of memory and hallucinatory daydreaming. But his body remained in excellent physical condition and he never became psychotic or lost contact with reality. After the experiment was over, he showed a small rebound, sleeping for nearly fifteen hours the first night and short extra periods on succeeding nights. This and many other similar experiments have convinced sleep researchers that it is primarily the brain and not the body that really gains from sleep. Similar conclusions have come from other studies, including carefully controlled animal experiments.

Why do we sleep?

Many issues in neuroscience remain an enigma and sleep is one of them.  Some people have argued that sleep is just a convenient way for animals to be kept immobile and so out of danger.  But there must be more to it than that. The sleep deprivation experiments lead us to think that REM sleep and certain phases of SWS enable the brain to recover.  We have this kind of sleep during the first 4 hours of the night. Perhaps it helps to reset things in the brain and that a good time to do this necessary task is, by analogy with a ship in dry dock, when the brain is not processing sensory information, or being vigilant and attentive, or having to control our actions.  Research also suggests that sleep is the time when we consolidate what we have learned the day before – an essential process in memory. 

How do rhythms work?

A great deal has been learned about the neural mechanisms of rhythmical activities such as sleep by recording the activity of neurons in various brain areas during the transitions between different sleep stages.  These have revealed a brain-stem activating system involving various neuromodulatory transmitters, including one called adenosine, in a kind of molecular chain reactionthat takes us through the various sleep stages.  Synchronisation mechanisms enable networks to pass from one sleep state to another.

A big leap forward has come from neurogenetics.  Various genes have been identified that, like the cog-wheels and escapement of a clock, are the molecular components of rhythmical pacemakers.  Much of this work has been done in Drosophila (fruit flies) where it has been found that two genes – per and tim- produce proteins that interact together to regulate their own synthesis.  mRNA and protein synthesis begins early in the day, the proteins accumulate, link up together and this linkage then stops their own synthesis. Daylight helps to degrade the proteins whose level eventually drops to a point where the genes that make PER and TIM protein get going again.  This cycle goes round and round, and will even carry on if the neurons are kept alive in a dish. 

The clock in mammals such as ourselves operates in a remarkably similar way to the one in flies.  As circadian rhythms are very old in evolutionary terms, it is perhaps no surprise that the same types of molecules drive the clock in such different organisms.

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