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MED2042 WEEK 2 - Neuroanatomy (Body rhythms and sleep and dreaming)


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What is the circadian rhythm?
Rhythms generated within the body and help coordinate the timing of our internal bodily functions as well as our interactions with the external world.

The regular cycle of light and dark, day and night that is the most pervasive recurring stimulus in the environment. It is the basis for fundamental adaptation of living organisms.
What does the circadian rhythm affect in mammals?
Variety of physiological and behavioural functions e.g. cycle of rest and activity, regulation of body temperature, metabolic rate, secretion of hormones and variations in psychomotor performance and sensory perception.
What are the two different patterns of timing for organizing behaviour into cycles of rest and activity?
In DIURNAL animals in which vision has evolved as the primary sense, activity typically occurs during daytime when vision best serves behavioural adaptation to the environment, and rest occurs at night.

For NOCTURNAL animals, in which olfaction and audition dominate perception of the environment, activity typically occurs during the night, and rest during the day.

In each case, the temporal order of behaviour has evolved so that activity and rest take place when the dominant senses can best aid feeding and the avoidance of predators.
How are circadian rhythms determined?
They are genetically determined and persist in the absence of environmental stimuli. They are a function of the nervous system and are generated by an intrinsic clock within the suprachiasmatic nuclei of the hypothalamus.

Recent research indicates that the circadian clock is made up of transcription/translational loops that involve a number of timing genes that are reciprocally turned on and off. In fact, cells excised from the suprachiasmatic nucleus and maintained in culture continue to show a circadian rhythmity in their activities.
What is the intrinsically generated rhythm in man?
The intrinsically generated rhythm has a time period of about 25 hours rather than the 24 hour lunar period.

The daily exposure to light entrains our intrinsic clock to the 24 hour lunar period. This entrainment stimulus is provided via an input from the retina to the suprachiasmatic nuclei.

If we were deprived of light, our intrinsic clock and body rhythms would steadily drift out of synchrony with the light-dark cycle.
What happens when circadian rhythm goes out of phase?
The disturbed mental and bodily functions of jet lag occur when we rapidly cross several time-zones, and our circadian rhythms become markedly out of phase with the day-night cycle of the new environment.

They symptoms reflect the delay in entraining the circadian pacemaker to the new time zone, and afflicted individuals experience nighttime insomnia and daytime sleepininess until readjustment takes place.

Non-24 hour sleep-wake disorder also commonly occurs in blind people whose circadian rhythms typically free-run with a period of about 25 hours since they lack visual input for entrainment. Normal-sighted people can also have poor or absent entrainment of their circadian clock which prevents them sleeping and waking at normal times.
What is sleep?
The phenomenon of sleep is trigeered by clocks in the brainstem, which are synchronized to the main circadian pacemaker in the hypothalamus.

Sleep is a behavioural state (a condition of altered consciousness) that alternates with waking. We spend approximately one third of our lives in sleep, where we are largely cut off from the sense of time and our environment, and are at our most vulnerable. During sleep, an animal cannot search for food, take care of its young, procreate or avoid the dangers of predation.
Why is sleep important?
The importance of sleep is suggested by the effects of sleep deprivation. If we are deprived of only one night's sleep, we do not perform optimally, the maintenance of wakefullness becomes increasingly difficult and the pressure to sleep becomes overwhelming. Prolonged sleep deprivation can lead to serious physical and behavioural problems.
What triggers sleep?
Sleep is an active process that is turned on or off by neural processes that involve the hypothalamus and brainstem.

The pressure to sleep depends on the intrinsic circadian rhythm that regulates body activity and the cyclic production and accumulation of chemicals that promote sleep.

The generation of sleep promoting factors is dependent on the sleep-waking cycle. These substances, that infiltrate the hypothalamus, are produced ruing waking and production declines during sleep.
What are two sleep promoting substances?
Adenosine and prostaglandin D2. Adenosine levels rise generally in the tissues during waking but prostaglandin D2 appears to be produced specifically by the pia and arachnoid.

Interleukin 1, produced byt eh immune system, has also been shown to be a sleep promoting factor. This could explain the excessive sleepiness associated with infections.
How is sleep monitored?
Sleep is assessed in research laboratories by monitoring "brain waves" or the electroencephalogram (EEG), which indicates the general state of electrical activity of the cerebral cortex.
How is the EEG in an active alert brain?
In an active alert brain, the elctrical activity of the EEG is low voltage and random or desynchronized.
What are the two main forms of sleep?
Slow wave sleep (SWS) with several stages where teh electrical activity increases in amplitude and synchronizes into waves.

Sleep with rapid eye movements (REM sleep) where the EEG is desynchronized, and closely resembles that of an alert brain.
How many stages does SWS occur in?
There are 4 stages of increasing depth of sleep in association with progressive synchronization of the EEG and changes in the body.
What stage of sleep do we first descend into? Describe what happens after.
At the start of a nights sleep we first descend into stages of deeper sleep.

Stage 1 SWS is the lightest sleep stage, where we just fall asleep and the EEG flattens and starts to show slower waves. We stay in this light stage of sleep for about 15 minutes and then progress to deeper stages of SWS.
What happens when we progress from stage 1 to 4 SWS?
The EEG progressively increases in amplitude and becomes more synchronized.

The body musculature progressively relaxes, brain activity decreases and oxygen consumption declines by about 40%. The heartbeat becomes slower and regular and breathing becomes slower, deeper and more even. Sympathetic activity declines and parasympathetic activity dominates.

We become progressively less responsibe to external stimuli, and less likely to awaken spontaneously or to be woke up by external stimuli as we descend into the deeper stages of sleep. However, even in stage 4 of SWS, we are not totally cut off from our bodies: we unconsciously adjust posture at regular intervals and sleepwalking occurs in this sleep stage.
What bodily changes have also been reported with SWS?
Increased hormone secretion, most growth hormone and sexual maturation hormones are secreted during SWS. The anabolic character of SWS with hormone release and brain and body inactivity suggests a rest and restorative function.
How is the SWS state switched on?
The SWS state is switched on by the reticular arousal system (RAS).

The RAS, which normally maintains the waking state, comprises a collection of nuclei in the rostral pons and midbrain.

These have widespread projections to the crerbral cortex and can also influence the cortex through projections to the thalamus and otehr nuclei in the basal forebrain.

The nuceli of the RAS employ noradrenaline/adrenaline, serotonin, acetylcholine and histamine as their neurotransmitters.

Theses arousal nuclei also receive excitatory input from the sensory systesm, which explains why it is difficult to fall asleep in a noisy environment or with a painful condition.
How long is the stage 4 SWS before the cycle reverses?
After some 30 or so minutes in stage 4 SWS, the sleep cycle reverses towards stage 1 and from this we enter a stage of sleep with rapid eye movements or REM sleep.
What happens when we switch to REM sleep?
When we switch to REM sleep, the EEG desynchronizes similar to that during waking. Brain O2 consumption increases and the heart rate and respiration become irregular. The body muscles come under active paralysis or inhibition via projections from the brainstem. Most of the body muscles are effected except for the respiratory muscles and the extraocular muscles, which are physically active moving the eyes around int he orbits (hence the term rapid eye movement sleep).

During REM sleep we are least responsive to external stimuli, but most likely to awaken spontaneously.
Describe dreaming in REM sleep.
Dreaming commonly occurs during REM sleep and this phase of sleep is often referred to as dream sleep. Dreams are generally active and colourful. Dreaming also occurs during SWS but less frequently and the dreams are generally introspective or oppressive and in black and white. Nightmares occur in stage 4 sleep.
How is REM sleep swithced on?
REM sleep is switched on via a REM sleep centre on the pons. This coordinates the events of REM sleep. It generates rapid eye movements, triggers muscle paralysis and causes brain activation through cholinergic projections to the cortex.

After a period of REM sleep we revert to SWS and go through several more cycles until we wake up, generally out of the last period of REM sleep.
How does sleep time with age?
Newborn infants spend about 14 hours in sleep in periods throughout the day. Total sleep time decreases overall by 1 year with a longer period occurring at night time. By about 4 years, most sleep takes place at night with just a short sleep in the mid afternoon. Children of age 5 and above essentially sleep only at night as do adults.

The very elderly gnerally revert to a childlike pattern of sleep and have a period of sleep in the afternoon.
How does sleep patterns change with age?
As we grow older teh amount of stage 4 sleep decreases and generally disappears entirely in old age. Also in old age SWS stage 3 declines and sleep is generally lighter with more spontaneous awakenings, particularly towards the end of a nights sleep.

REM on the other hand is maintained throughout life. The newborn spend about 80% of total sleep time in REM sleep. This declines quite rapidly with age to about 25% of total sleep time by late adolescence and it then remains constant at about this level for the rest of life.
Describe dreaming.
Dreaming can occur during any sleep state, but is most frequent during REM sleep. The dreams of REM sleep tend to be more vivid and active than those of SWS.

Most theories, which try to explain the role of REM sleep concentrate on dreams. There is as yet no well-accepted function for dreams although ideas go back to biblical times and forecasting the future and to Freud in the modern era where dreams were thought to be a means of dispelling internal conflicts.

However, detailed studies of many dreams have not revealed any evidence to suggest they help us to cope psychologically with the motional events expressed in the dreams.

Dreams do not necessarilty reflect much of real experience. Real emotions, people, places and events can be incorporated into dreams, but for the most part the content of dreams does not reflect reality and is an invention of the brain.

Some theories have attempted to put dreams in the physiological realm, suggesting they may be important in helping to clear out unwanted weak memory traces in the brain, or to reinforce and maintain essential or learned connections. However, there is as yet no experimental evidence to support these theories.

Very recently, it has been suggested that dreams themselves have a function otherwise they would have disappeared during evolution.

Dreams have been proposed to have survival value in that they simulate threatening situations. The brain conjures up potentially threatening situations and rehearses strategies to deal with them, right down to internally praciticing the appropriate motor responses. It is suggested that this internal simulation enables the brain to quickly recognize threats and select the best motor strategy for dealing with them.

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