L2 - Sleep part 2 PDF

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Sleep part 2 - how we sleep...

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Biological psychology L2 – Sleep part 2 1. What is sleep 2. Why do we sleep 3. How do we sleep 3. How do we sleep Cells of the nervous system • • •

Glia cells – majority of cells in the brain Neurons need glial cells to function Neurons – the processors of information – Within-cell communication: electrical (e.g. Action Potentials) – Between-cell communication: chemical (neurotransmitters)

Major sub-divisions of the brain

1. Forebrain splits into telencephalon and diencephalon a) Telencephalon is the cerebral cortex and basal ganglia b) Diencephalon is made up of thalamus (relay station for sensory info into the cortex) and hypothalamus (control of appetite, sleep, body temperature) 2. Midbrain is one part  Mesencephalon a) Tectum (roof) at top b) Tegmentum at bottom c) Canal in the middle of the brain is called the ventricles, which goes through the spinal cord as well and carries liquid.

3. Hindbrain splits into metencephalon and myelencephalon a) Metencephalon: i. Top becomes the cerebellum ii. Bottom becomes the pons b) Myelencephalon is made of the medulla 4. Rest of neural tube Arousal 5 main neurotransmitters (NTM): 1. Acetylcholinergic -

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There are 2 groups of acetylcholinergic neurons: o Metencephalon  in the Reticular Activating System in the Pons o Telencephalon  in the Basal Forebrain Stimulation of these neurons increases acetylcholine levels in the cortex AND increases alertness as well. Cholinergic antagonists make EEG more synchronized Cholinergic agonists desynchronize Cell bodies sit in pons and basal forebrain (brain stem) but the axons are so long that they cover most of the cortex therefore ACh is being released over most of the cerebral cortex

2. Noradrenergic -

From Locus Coeruleus in RAS in Pons High activity during waking, lower during sleep Related to vigilance, induced by external stimuli e.g., sudden knock at door Activity of LC is related to unexpected stimuli or paying attention to presence or absence of stimuli, not necessarily when grooming or drinking sweetened water.

3. Serotonergic -

From Raphe Nuclei (RAS in Pons and Medulla) High during waking, low during sleep Influence’s locomotion and cortical arousal, but not sensitive to external stimuli Driven by self

4. Histaminergic -

Electrical stimulation causes cortical arousal (EEG), while a drug which influences serotonin production decreases cortical arousal More active while awake, less (to nothing) while asleep Seem to be more involved in keeping ongoing activity going, rather than reacting to external stimuli

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They decrease their firing when an external stimulus (which would induce the noradrenergic system) arrives

5. Hypocretinergic - Neurons in the lateral hypothalamus use hypocretin as an NTM - Has excitatory (hypocretinergic) connections to the: o Locus coeruleus o Raphé nuclei o Tuberomammillary nucleus o Dorsal Pons o Basal Forebrain o Cerebral cortex - Active during active waking and exploration, inactive during sleep - Injection of hypocretin in these areas promotes activity and therefore wakefulness

Mechanisms of sleep induction -

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Ventrolateral Preoptic Area (vlPOA) in the Hypothalamus connects through GABAergic (inhibitory) synapses to: o Acetylcholinergic area of basal forebrain o Tuberomammilary nucleus (histamine) o Raphe nuclei (serotonin) o Locus coeruleus (noradrenaline) o Lateral Hypothalamus (orexin) Receives inhibitory input from most of these same brain areas Sleep is an active state of the brain Destruction of VLPOA leads to insomnia and DEATH Stimulation leads to drowsiness and sleep (including the EEG) Recording in VLPOA shows firing increases with drowsiness AND this is stronger when sleep deprived (see later: adenosine) Together, the vlPOA and the arousal system, make a system that is of 2 mutually inhibitory parts meaning when one is active it inhibits the other one and vice versa. Flip-flop is a system that is stable only in 2 mutually exclusive states It can flip from one state to the other either spontaneously (system is unstable), or through outside influence. Note, feature of flip-flop systems is that state changes go quickly: we’re either awake or asleep transitions are fast (is adaptive too) When the vlPOA is activated, it inhibits the arousal system and LH (lateral hypothalamus) orexinergic neurons. The LH itself does not directly inhibit the vlPOA, activation of the LH causes excitation to the arousal system which then inhibits the vlPOA. With these 3 systems alone, it would be quite stable but other external inputs also feed into the system.

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The LH is one of the places where different signals are integrated e.g. the LH is activated/excited by neuronal activity at a certain time of day (biological clock) – during the day i.e. light hours – and by hunger signals, hence it’s harder to fall asleep when you are hungry. When you are full, satiety signals are sent to the LH and inhibit it. The LH needs to measure up the difference between input to determine what input is having the biggest impact and determines activation/inhibition. During the day, the vlPOA is probably not active as the arousal system active meaning there is little inhibition of the LH. There is excitation of the LH due to biological clock and hunger signals so there is a very stable awake state. SLEEP  AWAKE: If you are asleep, when the morning comes along, your biological clock will start to excite the LH which in turn will start compensating for the inhibition of the LH from the vlPOA so the LH will become more active. This will start waking up the arousal system and allow it to start inhibiting the vlPOA and quickly you switch from being asleep to being awake. Because the hypocretinergic neurons are not involved in the mutual inhibition, they can bias the system to the “awake” state by activating the arousal system, and hence suppressing the sleep-promoting system We don’t know the input to the hypocretinergic system yet, so it’s just a vague reference to motivation at the moment.

Sleep can be induced by either adenosine or temperature. Adenosine: -

Adenosine: produced by astrocytes which use up their glycogen stores Increased levels of Adenosine cause more δ-activity during Slow Wave Sleep Adenosine has inhibitory effects on neurons

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Adenosine is a neurotransmitter and binds to adenosine receptors. Adenosine is a byproduct of the breakdown of glycogen (storage molecule). Glycogen is made up of many glucose molecules in a long chain which is broken down into glucose molecules and released in astrocytes for neurons to use for metabolism. Astrocytes are a part of glial cells and have these glycogen supplies. As the brain needs more energy, the glycogen is broken down to glucose which is used for energy for the neurons so the brain can continue to work. As adenosine is a byproduct of the breakdown of glycogen to glucose, more and more adenosine is created as the brain uses up more of its energy reserves stored in the astrocytes. This adenosine binds to adenosine receptors, and when there is more adenosine in the brain, you get more delta activity i.e., more SWS type activity in the EEG you see  the vlPOA has been activated. How does adenosine effect the vlPOA and switch the flip-flop from an awake state to an asleep state? Typically, when adenosine binds to its receptor on a neuron, that neuron will be inhibited. So, the membrane potential of that neuron will be hyperpolarized further away from action potentials.

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So, we have a NTM that builds up throughout the day making it more likely we will fall asleep and falling asleep activates the vlPOA yet the NTM is inhibitory.

2 theories for the adenosine reaction: -

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Disinhibition of vlPOA o The adenosine will be inhibiting neurons, but it might be inhibiting neurons which themselves normally inhibit the vlPOA  disinhibition of the vlPOA. o As there is less inhibition of the vlPOA, it is more likely to start firing action potentials. - Accumulation of adenosine inhibits neurons in the basal forebrain that inhibit the vlPOA - Therefore, inhibition of the vlPOA is blocked and so the vlPOA is more likely to start firing APs - This leads to a flip from an awake state to asleep state Inhibition of hypocretinergic neurons o There are adenosine receptors in the hypocretinergic neurons in the lateral hypothalamus o So, as well as disinhibiting the vlPOA, adenosine also inhibits the lateral hypothalamus (the master controller of the awake side of the flip flop) o As you go through the day and use your brain more, you use up your energy supply and adenosine build up. When a certain amount of adenosine is reached, the system flips to the asleep state allowing the adenosine to be cleared, glycogen stores to re-build up and so the brain is ready for more action the next day.

Temperature -

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Temperature of Brain and Skin o Sensed by another region in the basal forebrain o Higher temperature: • Inhibits acetylcholinergic basal forebrain areas • Inhibits tuberomammilary nucleus è induces sleepiness This could explain: • feeling of drowsiness when we have a fever • feeling of drowsiness on a hot summer day or a hot lecture theatre. An area in the basal forebrain senses higher temperatures. This area inhibits the acetylcholinergic basal forebrain and the tuberomammillary nucleus in the hypothalamus. There are neurons in the brain that detect temperature which are activated when the blood of the brain is at a higher temperature. When they are activated, they inhibit that area of the awake side biasing the system towards the sleep side. Example of how a system can be stable internally but impacted by external input

Onset of REM sleep

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During SWS our body temperature decreases. It is possible that there is a temperature threshold that when the BT goes below, causes the activation of the SLD. Once you go into REM sleep, the brain temperature increases again as it is so active. Once the temperature hits a certain threshold, this could cause the REM-on back off and you return to SWS. And this cycle is ongoing.

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Cholinergic agonists (like insecticides) increase REM, and antagonists decrease REM Some of the synapses involved at least are nicotinic. Same neurons responsible for arousal, but now with low serotonin and NA All are active during REM sleep (REM-ON cells), and some during wakefulness as well

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What happens once REM ON is activated, how does that REM ON area (the SLD) cause all the aspects of the REM stage? - Once REM sleep is activated, it activates the acetylcholinergic areas of the arousal system. During REM sleep, the different parts of the arousal system are acting in opposite directions. The noradrenaline and serotonergic area is very low in activity i.e. no neurotransmitter being released and no action potentials. Whereas the acetylcholinergic system in the basal forebrain and pons become very active (as during wakefulness) which drives the EEG which looks awake-like. - The pons also activates: - the lateral preoptic area (penile erection and sexual control) - the lateral geniculate nucleus in the thalamus  responsible for PGO waves - the neurons in the tectum (mesencephalon, controls eye movements)  hypothesis that REM are due to your response to the visual stimulation of the visual cortex i.e., your eyes are trying to look around the scene of your visual dream. - Muscle paralysis Evidence for muscle paralysis - Recording: active during REM only - Stimulation in subcoerulear or magnocellular area: paralysis - Lesion: still REM, but acted out - The implication of the fact that the inhibition of motor activity happens at so late a stage: in the spinal cord. This implies the activation of the motor system in the brain is necessary during dreaming/REM How does REM ON cause muscle paralysis? - The SLD (REM ON area) stimulates the magnocellular nucleus in the medial medulla. These cells in the medulla have very long axons which go all the way along the spinal cord and have inhibitory synapses on motor neurons which control the muscles. - Therefore, the paralysis of muscles that occurs during REM sleep is due to inhibition of the peripheral motor neurons. Sleep disorders Insomnia - Individual differences in sleep requirements

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Occurrence is overestimated i.e. people think they can’t sleep for much longer than the actual time e.g. take 15 mins instead of 10 to fall asleep Sleeping pills often make it worse Sleep Apnea Mostly self-report when investigating When actually measured, time to fall asleep is often not much longer in selfproclaimed insomniacs. Prescribing sleeping pills can lead to drug-dependent insomnia, because the body becomes physically dependent on the drug and cannot fall asleep without Sleep apnea: people who stop breathing when they fall asleep. This wakes them up again ften a physical problem with the airways and can be fixed surgically. Most people don’t get the amount of sleep they need but how much that amount is, differs between individuals. Sleeping pills take over some of the function of the flip-flop mechanism. Once you are used to having that drug in your system, it is much harder for you to sleep without them.

Narcolepsy - Narcolepsy  people fall asleep at unexpected times and randomly. - Sleep attacks: when someone is alert in a meeting then suddenly falls asleep, not just drifting off late at night. Often occurs when you are more excited. Leads you straight into REM sleep, not SWS. - Cataplexy  just the muscle paralysis, during the day (often brought about by strong emotions) without other symptoms of REM sleep. Therefore you are still alert and awake but cannot move your muscles; still aware of surroundings. - Sleep paralysis  same as cataplexy, but just before and after going to sleep, so no major consequences. - Hypnagogic hallucinations  dreaming while still awake (often right before falling asleep) and cannot move due to paralysis. -

Narcolepsy is often genetic, and that the system responsible has recently been worked out (involves Orexin or Hypocretin). Human narcoleptics show degeneration of the hypocretinergic neurons. Narcoleptic dogs show an inherited absence of hypocretin-2 receptors.

REM Sleep Behaviour Disorder - No paralysis during REM sleep - Acting out of dreams - Genetic or damage to brain stem Problems during SWS - Bedwetting  Mostly in children, lost of bladder control in SWS - Sleepwalking  Need muscle tone to be able to walk therefore must occur in SWS unless have REM without atonia - Night Terrors  Mostly in children

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Sleep-related eating disorder  combination of sleep walking and eating....