8 - Physiological Basis of Sleep and Arousal II Flashcards

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1
Q

Where are the histamine nuclei involved in the regulation of sleep? What are they called?

A

Nuclei near hypothalamus (forebrain structure)

  • Tuberomammillary nucleus (TMN), only place in brain that produces histamine
  • Activating projections all over cortex (direct) and basal forebrain (indirect activation)
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2
Q

What is the common function of the Tuberomammillary nucleus (TMN)?

A

One of the most important arousing neurotransmitters

- Activating projections all over cortex (direct) and basal forebrain (indirect activation)

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3
Q

What happens when histaminergic Tuberomammillary nucleus (TMN) is destroyed?

A

Increased sleep, such as with African Sleeping Sickness.

Without histamine, unable to become alert for significant periods of time. Squirting histamine onto neurons activates neurons.

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4
Q

How does adenosine interact with histamine?

A
  • Adenosine inhibits activating histaminergic neurons
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5
Q

Why were antihistamines developed? What was the effect of ones that could get in the brain?

A

Histamine is produced by basophils and mast cells in the immune system to be released for allergic reaction or in stomach lining, where it triggers acids that help in digestion (too much leads to ulcers).

If antihistamines block histamine transmission in brain, they make you drowsy. Combined now with analgesics (eg acetaminophen) for sleeping pills, though this can lead to tolerance, daytime drowsiness and heart issues.

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6
Q

What is orexin and hypocretin?

A
  • Orexin named for producing food intake
  • Hypocretin named for secretin in hypothalamus

SAME CHEMICAL, but two different words for it :S

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7
Q

Where is hypocretin found? Where does it project to?

A

The hypothalamus

Hypocretin neurons cluster around the fornix mammillary bodies (perifornical) and project to every part of the nervous system.

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8
Q

What happens when you apply hypocretin to cells?

A

Alerting and activating effect

Decreases probability of transitioning to REM sleep by activating REM-OFF cells (NE and 5-HT), which prevents cholinergic system from activating REM onset.

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9
Q

How does hypocretin affect REM sleep?

A

Decreases probability of transitioning to REM sleep by activating REM-OFF cells (NE and 5-HT), which prevents cholinergic system from activating REM onset.

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10
Q

What happens if you have a histamine KO mice?

A

Inject hypocretin into ventricles and you won’t get arousal. The effects of hypocretin are mediated through histaminergic neurons.

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11
Q

When are hypocretin levels elevated?

A

During waking (especially at last hours before sleep). Might help you fight against homeostatic drive for sleep.

Not as elevated when the animal is awake, but quietly. Movement associated with it.

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12
Q

What other things besides sleep does hypocretin participate in? What connects all these?

A
  • Food intake
  • Addiction
  • Reward mediation etc.
  • Learning
  • Stress

All have to do with arousal/all need arousal to respond/do these things. Hypocretins role in sleep might be a reflection of its broad arousal effects in other motivational states.

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13
Q

When hypocretin neurons are optogenetically inactivated, what is observed in the dark/light phase in mice?

A

Dark phase: no big effect
Light phase: instant slow wave sleep

This is thought to be because of high levels for other activating neurotransmitters during dark phase, and no relative inhibition for sleep in light phase.

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14
Q

What type of cells are mixed in with hypocretin cells in the hypothalamus? What is their effect?

A

Melanin-concentrating-hormone (MCH) expressing cells. Contain GABA and promote REM sleep by inhibiting REM-OFF neurons and particularly inhibiting hypocretin neurons nearby

Become very active whenever the animal is producing REM sleep or during recovery sleep.

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15
Q

What is insomnia? What are two core symptoms?

A

Individuals fall asleep in unusual circumstances. Different racial groups have different proportions from inbreeding (suggesting genetic link).

  • Excessive daytime sleepiness (narcolepsy is sometimes not diagnosed for a looooong time because of this)
  • Irresistible sleep attacks with little or no warning in any possible type of arousing situation, cataplexy (loss of motor control, form of paralysis, not sleep). If general, collapse, though weakness in certain muscles is possible too.
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16
Q

What happens when you optogenetically silence hypocretin neurons in the lateral hypothalamus?

In dark phase?
In light phase?

A

Dark: Nothing
Light: Immediate entry into SWS

This could be due to ending serotonergic arousal or other NTs having a larger role in arousal during dark phase.

17
Q

What is melanin-containing hormone (MCH)?

A
  • Peptide that is linked to food intake, energy balance and sleep regulation

Inactive during waking
More active during nREM
Very active during REM!

MCH neurons commonly have GABA to promote REM sleep, inhibit hypocretin neurons and other REM-OFF neurons