Lecture nine - Sleep Neurobiology

Question 1

What are aminergic neurons?

Answer 1

Neurons that release serotonin, dopamine, or noradrenaline.

Question 2

Is there one part of the brain responsible for wakefulness?

Answer 2

No. There are multiple brain regions that are engaged to bring about wakefulness.

Question 3

What areas of the brain have been associated with the wakefulness system?

Answer 3

The acetycholinergic (neurotransmitter is acetylcholine) neurons in the LATERODORSAL TEGMENTAL NUCLEI (LDT), PEDUNCULOPOTINE TEGMENTAL NUCLEI (PPT), and the BASAL FOREBRAIN (BF).

The monoaminergic neurons in the:
LOCUS COERULEUS (noradrenergic neurons specifically).

DORSAL AND MEDIAL RAPHE NUCLEI (serotonin - 5HT - producing specifically).

TUBEROMAMILLARY NUCLEUS (TMN) (histaminergic neurons specifically).

VENTRAL PERIAQUEDUCTAL GREY MATTER (PAG) (dopaminergic neurons specifically).

PARABRACHIAL (PB) and PRE-COERCULEUS (PC) (gluatminergic neurons specifically).

Question 4

What areas of the brain associated with the wakefulness system are acetycholinergic (produce acetylcholine)?v

Answer 4

LATERODORSAL TEGMENTAL NUCLEI (LDT)
PEDUNCULOPONTINE TEGMENTAL NUCLEI (PPT)
BASAL FOREBRAIN (BF)

Question 5

What areas of the wakefulness system are monoaminergic?

Answer 5

LC - serotonin
Raphe nucleus - serotonin
TMN - histamine
PAG - dopamine
PB and PC - glutamine

Question 6

Is it true that neurons in the LDT, PPT and BF release acetylcholine that acts on the cortex via the thalamus?

Do the the monoaminergic neurons also act through the thalamus?

Answer 6

Yes.

Yes, although not only through the thalamus??

Question 7

In studies in rats and mice, what is the pattern of firing in cells in the LC across the wake and sleep cycle?

Answer 7

Neurons fire when awake, with levels decreasing as animal drops into sleep. In REM sleep firing almost decreases completely, and then increases when animal awakes.

Question 8

Why do long-haul truck drivers take amphetamines?

Answer 8

Amphetamines increase the production or availability of noradrenaline. Noradrenaline increases wakefulness.

Question 9

What neurotransmitter controls wakefulness in the brain?

This neurotransmitter ensures that all areas associated with wakefulness, such as the raphe nucleus or locus ceroeleus, are being activated. This helps to ensure that all areas of the brain required for wakefulness are awake and we don’t have different areas going to sleep at different times.

Answer 9

OREXIN (aka hypocretin).

Question 10

What is OREXIN?

Question 11

What area of the brain produces OREXIN?

Answer 11

Neurons in the lateral hypthalamus.

Question 12

What increases orexin production?

Answer 12

During active exploration.
Low glucose levels.

Question 13

What area of the brain is considered to be the master controller of wakefulness?

What neurotransmitter do these neurons produce?

Answer 13

Neurons located in the lateral hypothalamus produce orexin and orexin ensures the required brain areas and the cortex are ‘awake’.

Question 14

How does the sleep system work (broadly)?

Answer 14

Neurons in the VENTROLATERAL PRE-OPTIC NUCLEUS (VLPO) produce GABA and GALANIN, which are inhibitory neurotransmitters, and these inhibit the areas of the brain associated with wakefulness, such as the raphe nucleus and the locus ceroeleus.

The VLPO also inhibits the oxerin-producing neurons in the lateral hypothalamus.

Question 15

When are VLPO neurons active?

Answer 15

They are only active during sleep.

Question 16

Does VLPO neural activity increase with sleep deprivation?

Answer 16

No. Sleep deprivation does not increase VLPO activity. VLPO neurons will only fire during sleep.

Question 17

There are two VLPO regions which are responsible for different types of sleep.

When there are lesions in the VLPO cluster, what type of sleep does the animal get less of?

When there are lesions in the extended VLPO, what type of sleep does the animal get less of?

Answer 17

When there are lesions in the VLPO cluster, animals get less non-REM sleep.

When there are lesions in the extended VLPO, animals get less REM sleep.

Question 18

Are there multiple sleep-promoting areas in the brain?

Answer 18

Yes.

Question 19

What is SAPER’S FLIP-FLOP switch model for sleep and wake states?

Answer 19

Levels of OREXIN control whether the brain is awake or asleep.

When orexin levels are low enough and there are sufficient circadian signals the switch is turned “on” and the VLPO regions inhibit the production of orexin or the signalling of the wakefulness areas, such as the Raphe nuclei, inducing a state of sleep.

When orexin levels are high enough and the required circadian signals are present, the switch is turned “off”. VLPO regions are inhibited and orexin and the wakefulness areas are able to signal to the brain to wake.

Question 20

What is the BASIC REST ACTIVITY CYCLE (BRAC)?

Answer 20

BRAC refers to the roughly 90-minute cycle of alertness and fatigue. We go through these cycles during wakefulness as well as when we are asleep, It can be seen when we are asleep as NREM sleep and REM sleep.

Question 21

do vlpo neurons only fire when sleep occurs?

Answer 21

yes.

Question 22

what causes us to fall asleep then?

Answer 22

The Median Pre-Optic Nucleus (MnPO nucleus).

The median pre-optic nucleus is located next to the the VLPO region and projects to the VLPO neurons (although that doesn’t make much sense), the lateral hypothalamus, raphe, LC and PC. As we become more tired neurons from the median pre-optic nerve fire more frequently. Their neurotransmitter is GABA, an inhibitory neurotransmitter. This inhibits the wakefulness functions of the raphe, LC, PC, and lateral hypothalamus, inducing sleep.

Question 23

What wakefulness areas does the median pre-optic nucleus not project to?

Answer 23

The PPT, LDT, and TMN.

Question 24

What are the suprachiasmatic nuclei?

Answer 24

They are a set of two nuclei located in the anterior part of the hypothalamus. The SCN regulates circadian rhythms. Signals from the melanopsin retinal ganglion cells are sent to the SCN to inform it of levels of light.

Question 25

How do circadian rhythms (process C) control sleep?

Answer 25

The SCN does not have direct connection with the VLPO regions or the wakefulness regions, however, it indirectly projects to these regions via the subparaventrical zone (SPZ), which in turn connects to the dorsomedial hypothalamus (DMH), and in turn projects to the VLPO regions, orexinergic neurons.

Question 26

What is a polysomnogram?

Answer 26

A polysomnogram is the trace one gets when using an EEG, EOG, and EMG to measure sleep/wake cycles.

A hypnogram refers to the length of sleep cycles across a night of sleep as measured by a polysomnogram.

Question 27

How many phases of sleep are there?

Answer 27

4.
NREM 1,
NREM 2,
NREM 3,
REM.

Question 28

Is orexin a neuropeptide made from the genome of the organism?

Answer 28

Yes.