topic 6 - sleep

Question 1

how does the vlPOA have mutual inhibition?

Answer 1

vlPOA has a reciprocal relationship with the brain areas that it inhibits during sleep. these areas inhibit the vlPOA during the wake
flip-flop

Question 2

describe the mechanisms of transitioning to sleep (ventrolateral preoptic area vlPOA)

Answer 2

the ventrolateral preoptic area is located in the hypothalamus and is active when asleep. organisms are unable to fall asleep without this and would die. the vlPOA connect to other areas of the brain (acetylcholinergic area of the basal forebrain, raphe nuclei - histamine, locus coeruleus - noradrenaline, lateral hypothalamus - orexin) through GABA-ergic inhibitory synapses. recieves inhibitory input from most of these brain areas. stops activity in areas of the brain which keep use alert and awake

Question 3

describe REM sleep

Answer 3

• high activity in the brain
• loss of muscle tone = paralysis
• penile erection/vaginal secretion
• clear narrative dreams
  –> pontine-geniculate-occipital (PGO) waves which is the area of the brain related to sight causing visual dreams

Question 4

how is REM sleep controlled

Answer 4

• second mutual inhibition between sublaterodorsal nucleus (SLD) in dorsal pons (REM ON) and ventrolateral peri-aqueductal gray matter (vlPAG) in mid-brain (REM OFF)

Question 5

Describe that one complex diagram of REM sleep

Answer 5

LH orexinergic neurons excite the ventrolateral peri-aqueductal during the day so then REM OFF is maintained. these neurones are excited by hunger signals and bio clock-time of day. the locus coeruleus and raphe nucleus inhibit REM ON (sublateraldorsal nucleus) using noradrenaline and serotonin. only when these brain regions are low in activation can the flip flop occur and REM ON be active. the ventrolateral preoptic area inhibits REM OFF during sleep

Question 6

what do REM ON neurones indirectly affect?

Answer 6

 Acetylcholinergic basal forebrain: EEG changes
 Acetylcholinergic pons, which:
 Activates the lateral preoptic area – penile erection
 Directly activates lateral geniculate nucleus in the thalamus  PGO waves
 Activate neurones in the tectum – mesencephalon – rapid eye movements
 Muscle paralysis

Question 7

explain muscle paralysis

Answer 7

sublateraldorsal nucleus sends signal to the magnocellular nucleus which inhibits the spinal motor neurones
magnocellular nucleus only responsible for for the paralysis aspect of REM sleep - damage causes REM sleep behaviour disorder

Question 8

what is the activation-synthesis hypothesis

Answer 8

• dreams are the brain trying to make sense of the day
• combination of external and internal stimuli which the brain uses to synthesise a story

Question 9

what is the sleep-wake flip flop influenced by?

Answer 9

• homeostatic control - maintaining a working system
• allostatic control - over-ride in case of danger
• circadian control - controls sleep relative to the day-night cycle

Question 10

homeostatic control of sleep and adenosine

Answer 10

adenosine is produced by astrocytes which use up their glycogen stores
- neurones need sugars not fat adenosine stores glycogen which can be broken down in to glucose
- adenosine has inhibitory effects on neurones
- ATP is adenosine triphosphate
- accumulate more adenosine throughout the day and this build up slowly causes the onset of slow wave sleep

Question 11

what are the two hypotheses for adenosine action?

Answer 11

disinhibition of the vlPOA
- prolonged metabolic activation of neurones in the brain causing an accumulation of adenosine
- this inhibits the neurones in the basal forebrain which inhibit the ventrolateral preoptic area.
- therefore the inhibition of the ventrolateral preoptic area is removed allowing the sleep-promoting region of the vlPOA to be activated and inhibit the waking mechanisms
genetics
- adenosine broken down by adenosine deaminase
- enzyme exists in at least2 versions
- G/A genotype works slower than G/G genotype
- G/A people need 30mins more short wave sleep

Question 12

explain brain recovery theory of slow wave sleep

Answer 12

• short wave sleep affected by increases in brain temp
• short wave sleep affected by mental exercise
• metabolic breakdown products cleared during short wave sleep due to this process of resting and recovering the brain

Question 13

allostatic control of sleep: response to hunger

Answer 13

• threats to survival promotes wakefulness
• there are 2 hormones which signal hunger: leptin and ghrelin
• leptin inhibits hypocretinergic neurones
• leptin signals full fat stores and makes it easier to sleep
• hypocretinergic neurones are stimulated by ghrelin signalling an empty stomach. the more stimulation the harder it is too fall asleep

Question 14

response to stress sleep/wake flip flop

Answer 14

areas which are responsible for the stress response also stimulate parts of the arousal system
sensory stimulated activates hypocretinergic and noradrenergic neurones. the medial prefrontal cortex has excitatory synapses on hypocretinergic and noradrenergic neurones. these neurones are also excited by corticotropin releasing factor from the central extended amygdala

Question 15

what is the endogenous clock?

Answer 15

• an internal clock which keeps cycle going even without external stimuli located in the suprachiasmatic nucleus
• when the SCN isnt present will sleep the same amount just not in 2 chunks

Question 16

rat studies on suprachiasmatic nucleus

Answer 16

• lesion studies
• when cells removed from the hamster and kept alive activation could be seen even when cells separated from each other still maintained a rhythm
• transplantation studies found hamster with 20hr rhythms and when this was put into a 24hr hamster the 24hr hamster turned into a 20hr hamster

Question 17

molecular mechanisms of circadian rhythm

Answer 17

involves 3 period genes (per 1 to 3), 2 cryptochrome genes (cry 1 and 2), clock and Bmal genes
- clock and Bmal proteins bind together in the nucleus and stimulate the genes to trascribe DNA in mRNA of per1-3 and cry
- mRNA then leaves the nucleus and goes to the ribosomes to be translated into proteins
- a cry and a per find each other to create either cry+per1/3 or cry+per2 complexes
- these complexes return to the nucleus
- cry+per1/3 suppresses the function of the CB complex and less DNA is transcribed into RNA and less protein is made - stops its own start
- cry+per1/3 peaks in 12hr cycles due to a negative feedback loop

Question 18

circadian control of sleep: from suprachiasmatic nucleus to flip-flop

Answer 18

• suprachiasmatic nucleus excites the ventral subparaventricular zone which excites the dorsomedial nucleus of the hypothalamus
• this inhibits the vlPOA exciting the lateral hypothalamus

Question 19

how do biological rhythms synchronise with the world?

Answer 19

• zeitgebers are time givers which entrain the internal rhythm with the external rhythms
• examples are light, food and sounds
• short light pulses can reset the clock
• light in the beginning of the night cycle can extend wakefulness
• and light late in the night can bring wakefulness foward

Question 20

mechanisms to rest the clock

Answer 20

1) direct projection from melanopsin-containing retinal ganglion cells in the SCN
2) indirect projection from the retina to the SCN via the lateral geniculate nucleus
3) retino-hypothalamic tract (RHT) axon synapses go onto the SCN using glutamate onto NMDA-receptors
- causes an increase in intracellular calcium and induction of 2nd messenger cascades

Question 21

how is the circadian rhythm synchronised across the body?

Answer 21

• activity of the SCN during the subjective day suppresses the activity of the sympathetic superior cervical ganglion
• during the night, sympathetic activity releases noradrenaline onto the pineal gland triggering synthesis of melatonin and tis release into the blood stream

Question 22

what are the two effects of melatonin receptors in the SCN?

Answer 22

1) acute inhibitory effect on neuronal firing
2) phase-shifting effect of rhythm - especially within 30 mins of onset of subjective night
- does not directly affect transcription of Per and Cry but does interact with the cycle via other mechanisms

Question 23

insomnia

Answer 23

• some peop need more sleep than others
• bad predictors of time therefore occurrence overestimated
• sleep pills make worse
• linked to sleep apnea

Question 24

narcolepsy

Answer 24

• usually to do with lateral hypothalamus
• includes sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucination
• cataplexy - sleep attack isnt suddenly falling asleep but rather jumping straight to REM and being paralysed but awake and aware of surroundings

Question 25

rem sleep behaviour disorder

Answer 25

- lack paralysis - magnocellular nucleus damage - acting out dreams and become danger - sleep walking occurs during slow wave sleep so this is different