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47 Cards in this Set
- Front
- Back
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I missed notes from the second slide because i was late for class |
get from Becca |
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everything from this lecture is used to support that sleep is an active, brain generated process |
mm |
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what did F. Bremer do? (1930) |
he studied the effects of brain lesions on sleep waking states |
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what did he discover when he did lesion #1(cut junction of medulla and spinal cord) |
when he did this lesion, the sleep wake cycle remained intact |
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what did he discover when he did lesion #2 (cut at midpontine level) |
subjects showed chronic wakefulness and insomnia |
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what did he discover when he did lesion #3 (isolated the forebrain by cutting midbrain between sup and inf colliculus) |
chronic slow wave sleep |
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what are the 4 conclusions from Bremer's work? |
1) brain stem contains important centers for the regulation of sleep and waking 2) upper brain stem contains neurons that promote waking 3) lower brain stem contains neurons that promote sleeping 4) these experiments show that sleep is an active process, not just a default state in the absence of waking (basically it shows that there are actual brain centers that promote sleeping, sleep isnt just caused by the shutting off of waking centers) |
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Prof's conclusions of Bremer's work: |
- there is still a lack of literature on this, the sleep centers in the brain havent been totally localized yet - Bremer may be wrong about the location of the sleep centers in the brain - BUT he did contribute by showing that sleeping is an ACTIVE process |
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Describe the experiment by Moruzzi to try and localize sleep wake centers in the brain |
- instead of doing lesions, he put an electrode in the brain of anesthetized cats and used the electrode to stimulate this brain region - he put this electrode in the reticular formation, in the brain stem results: when he stimulated the reticular formation, the EEG showed a change from slow waves to active awake waves (when the reticular formation was stimulated it resulted in fast desynchronized waves in the EEG) electrical stimulation of RF => EEG arousal response in anesthetized animals |
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what do the results of this study show? |
it supports that the reticular formation is the main waking system of the brain |
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what did they find when doing further experiments with animals and the reticular formation? |
they did a study with animals, they looked at the animal's EEG waves when he was asleep, and then they made a loud noise and they looked at the animal's EEG wave when he now became awake from the loud noise in the other condition: they looked at the animal's EEg waves when he is asleep, and then they stimulated the reticular formation and examined the changes in EEG waves results: they found that when the reticular formation was stimulated the following brain waves matched the brain waves that occured after hearing a loud sound electrical stimulation of RF => mimics natural awakening in behaving animals |
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they also did studies where they damaged the reticular formation in animals what happened when the reticular formation was damaged in animals? |
coma or death |
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so conclusion from these studies: |
Conclusion: the brainstem core contains neural circuity that is highly important for the regulationof sleep and waking states and the related EEG phenomena |
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go to slide 7 to see an image of the anatomy of the reticular formation |
mm |
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what are the three classes of neurons for sleep and wake |
- waking neurons - Sleep ON neurons - REM ON neurons |
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what are the waking neurons? |
5-HT (serotonin, raphe nuclei) NA/A (noradrenaline/adrenaline, locus coeruleus) histamine (tuberomammillary nucleus of hypothalamus)
orexin (hypothalamus) ACh (acetylcholine, basal forebrain and pontine tegmentum) (most of these neurons are spread throughout the reticular formation) (most or all of these neurons contain a neurotransmitter called serotonin - serotonin is a transmitter that makes you wake up) some of these neurons are also REM off neurons |
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what are the sleep ON neurons? |
(they arent really found in the reticular formation - they are found at the end of it, see slide 9) sleep ON neurons are neurons that help you go to sleep, and include: - ventral and medial preoptic area - thermosensitive: heating -> sleep - inhibit waking neurons |
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what are the REM ON neurons? |
- ACh neurons in the brainstem Thermosensitive: Cooling -> REM sleep |
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what are the different experimental approaches used to identify sleep-wake brain systems How can we determine the behavioural or other functions of specific brain systems? (this could deff be an essay question) |
experimental strategies: - measure brain activity (neuronal, metabolic, blood flow) -> correlation with sleep/waking? - effects of specific neural damage or inactivitation -> does it result in changes to sleep/waking (I assume this is case studies) - pharmacological manipulations (agonism or antagonism) -> does this lead to changes in sleep or waking? ex: if you use a serotonin antagonist drug does this lead to changes in sleep and waking.. the prediction i think would be that the drug would lead to increase in sleeping - genetic manipulations (gene knock our or over expression) -> does this lead to changes in sleep and waking - clinical studies (ex: we know that serotonin is abnormal in people with major depression) - comparative approaches (ex comparing animal studies to human studies , i think) |
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what is an example of a study to examine neuronal activity across the sleep-wake cycle |
measure EEG, EMG, action potentials and movement in a rat of sleep wake cycles what did the results of this stud show: EEG - slow waves during sleep and fast desynchronized sleep during wake EMG - movement during wake, no movement during sleep Action potentials for neurons that fire serotonin - there were a lot of these action potentials during waking, but barely any during sleeping (this supports the hypothesis that serotonin is associated with waking) HOWEVER we cant conclude conclusively that - serotonin CAUSES the animal to wake up because we are only looking at a correlation here - we don't know the direction of the relationship (it could be that there are other neurons that cause you to wake up, and then once you are awake those other neurons also cause serotonin to be released) so there are limitations to this corerlational study of neuronal activity across the sleep-wake cycle |
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describe a study that looked at the activity profile of 5-HT neurons in the Raphe Nuclei over the sleep wake cycle |
they found that during the stages of sleep the 5-HT neurons fired less and less¸ but as soon as REM sleep ended activity profile of 5-HT neurons increased A LOT this again suggests that when you wake up from sleep there is a burst of activity in the neurons that release serotonin so it seems that serotonin influences wakefulness - but again this is just a correlation - not cause and effect! |
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describe results from other correlational studies that looked at wake ON neurons other than 5-HT |
they tracked the firing of different neurons at different stages of sleep and waking results: NA (noreadrenaline) fires when you are awake and stops firing when you are asleep histamine is not active when you are asleep but it becomes active when you are awake ACh (acetylcholine) not active when asleep, but yes active when awake they also found that the preoptic area is active when asleep, but not active when awake (this is one of the Sleep ON neurons proposed) |
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make sure i dont need to know slide 14 that he skipped |
mm |
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how do neurotransmitters/modulators induce brain activation and waking behaviors? describe a study that shows this system wide effect - for the waking promoting effects of serotonin (5-HT) |
what do the results show when 5-HT is stimulated in the brain? 5-HT has a dual role: - it wakes up your whole forebrain - and it inhibites activity in both sleep centers (the VLPO which is sleep promoting and the PONS-ACh which is REM sleep promoting) |
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what are some other effects that also come from 5-HT? |
- excitation of histamine neurons - depolarization of cortical pyramidal cells - and other effects and this is how 5-HT wakes up the whole forebrain (the other part of the dual role that 5-HT does) |
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what happens the longer you are awake? (with regards to 5-HT) |
the longer you are awake the less that 5-HT fires, which reduces the inhibition of the two sleep centers, which makes you feel more and more tiered until you decide to go to sleep) |
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to review, what are the two sleep centers: |
VLPO - sleep promoting PONS-ACh - REM sleep promoting |
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how do neurotransmitters/modulators induce brain activation and waking behaviors? describe a study that shows behavioral effects - describe the study that looked at orexin |
study that shows the waking-promoting effects of orexin: previous studies that looked at how manipulations effect behavior often used electrical stimulation to a specific neuron by using and electrode, but the problem with this is that you have less good control because it also stimulates the neurons surrounding that neuron a little bit as well so what was a better technique that they used: - they used light technology (when the light was directed at the animal it caused that specific target neuron to fire) they did this by injecting a virus into the animal that attaches to that specific neuron and is senstivie to light so what were the results of the study: - they found that when they stimulated orexin neurons it induced waking behavior in the animal Activation of orexin neurons during slow wave sleep (SWS; top two traces) or REM sleep (bottomtwo traces) results in waking |
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the light technique is a very good way of looking at the causal effects of neuron activation in the brain |
mmm |
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what the implications of the results of this study? |
-orexin neurons also act as a hunger signal so it could be that there is a system in the brain that kicks in powerfully if you need a lot of energy and you need to wake up to find food Metabolic hunger signals (e.g., glucose, neuropeptide Y) => orexin activation => increased waking |
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describe the results of the artificial data that shows what happens when you administer: -NA lesions - NA depletion (the artificial data here summarizes the real results of many different studies - subject is a horse here) |
before the lesion: sleep/wake is normal 2 days after the lesion to NA: sleep increases (this is because NA is important for waking up) 1 month after the lesion to NA: sleep/wake cycles are back to normal |
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what is this explanation for the sleep/wake cycle bouncing back to normal? |
- there are other neurotransmitters that are involved in waking us up - so these other neurotransmitters have compensated for the lack of NA in the brain so it is very adaptive for us to have many systems in the brain that help us wake up - because if we have damage to one of those systems we will still be able to wake up, we wont be stuck asleep/in a coma forever and so that is probably why we have so many systems in the brain that help us wake up |
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summary: what are the four important points for brain systems involved in wake regulation? |
1) waking is regulated by varying levels of cellular activity in specific, widely distributed neuronal groups in the forebrain, midbrain and pons (reticular formation) 2) Numerous transmitter classes are involved in wake regulation 3) No single system is essential! (if one waking system is destroyed the other waking systems will compensate for it) 4) consequently, there is no strict "localization of function |
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sleep is an active process, explain: |
there are specific systems in the brain that make you go to sleep |
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what are the four stages of slow wave sleep (non-REM sleep): |
Stage 1: EEG similar to "drowsy waking" Stage 2: Sleep spindles and K-complexes Stage 3: appearance of delta waves Stage 4: Delta waves become prominant |
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the systems for sleep are more in the front of the brain |
see slide 20 |
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what generates slow wave sleep? |
- The Ventral Preoptic Area (VIpo) - The Medial Preoptic Area (Mpo) |
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what is evidence for the Ventral Preoptic Area as a center for sleep ? |
- brains of patients with insomnia show pronounced damage to the preoptic area of the basal forebrain (Case studies) - administering preoptic lesions in cats causes insomnia (experimental manipulation) - warming of the preoptic area induces sleep - the preoptic area contains many GABAergic and galanin-containing neurons (this neurons have inhibitory effects -so they help inhibit the waking centers in the brain during sleep) - neurons in the vental preoptic area are active during sleep (correlation) |
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what is evidence for the Median Preoptic Area as a center for sleep ? |
- similar activity and neurochemical profile to VPA (sleep-active neurons, and contains GABA) - neurons in the Mpo inhibit wake-active cell populations - when the Mpo is deactivated it leads to long lasting insomnia - excitation of the Mpo leads to slow wave sleep - neurons in the Mpo become more active during sleep deprivation |
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how do these two sleep systems (VIpo and Mpo) interact? |
Mpo (median preoptic area) - influences sleep pressure and onset - the activity of the neurons in this system builds up sleep pressure - this system helps you fall asleep VIpo (vental preoptic area) - responsible for sleep maintenance and duration - this system helps you stay asleep (this system maintains and keeps you asleep throughout many hours) - once sleep occurs, the VIpo becomes more active throughout the night see slide 22 to see this change in activation of these two systems throughout the night and PRACTISE DRAWING IT |
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elderly people who had trouble sleeping
what did the correlation show |
loss of neurons in the ventral preoptic area correlated with increased trouble sleeping and remember that the ventral preoptic area is a system used to maintain sleep |
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what is the "Flip Flop Model" proposed by Clifford Saper |
Various wake- and sleep-related neuronal groups are closely interconnected, allowing them toinfluence each other. this model explains the regular cyclic alternations in sleep and waking states - when the waking system is active it dominates the whole system and inhibites the sleeping system - when the waking system shuts down it stops inhibiting the sleeping, and the sleep system also becomes more active because of heat and fatigue - and so this sleep system now takes over review slide 24 to see the diagram this could be a good exam question |
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where is serotonin found in the brain |
raphe nuclei |
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where is adrenaline/noradrenaline found in the brain |
locus coeruleus |
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where is orexin found in the brain |
hypothalamus |
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where is histamine found in the brain |
tuberomammillary nucleus of hypothalamus |
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where is achetylcholine found in the brain? |
basal forebrain, pontine tegmentum |
