Neurophysiology Of Sleep

Front 1

What regulates alertness?

Back 1

1. RAS

Front 2

What regulates attention?

Back 2

1. RAS

2. Supratentorial processes

Front 3

What is the effect of increasing levels of adenosine in the brain?

Back 3

1. Sleep inducement

Front 4

What NTs control wakefulness?

Back 4

1. ACh

2. NE

3. Dopamine

4. Serotonin

5. Histamine

6. Orexin/hypocretin

Front 5

What NTs modulate sleep?

Back 5

1. GABA

2. Adenosin

3. Galanin

4. Melatonin

5. MCH (REM)

Front 6

How is GABA involved in wakefulness?

Back 6

1. Inhibition of neurons that inhibit cortical activity

Front 7

Where are ACh pathways found?

Back 7

1. PPT

2. LDT

3. Basal forebrain

Front 8

What is the role of the cholinergic projections to the hippocampal formation?

Back 8

1. Generate a rhythmic oscillation--- hippocampal theta rhythm

2. Plays a role in memory functions of the brain

Front 9

What are the functions of ACh in the brain?

Back 9

1. Facilitation of attention, memory, and learning

Front 10

What is the effect of pharmacological blockade of cholinergic transmission?

Back 10

1. Delirium

Front 11

How does ACh increase neuronal activity?

Back 11

1. Activation of nicotinic a4B2 and a7 receptor channels

2. Activation of M1 and M3 receptors

Front 12

What is the function of a4B2 and a7 receptors?

Back 12

1. Nonselective cation channels

2. Allow Na and K to move through

3. Activation depolarizes the neuron

Front 13

What is the function of M1 and M3 receptors?

Back 13

1. Ligand-activated

2. Inhibition of Kv7

3. Depolarizes resting membrane potential

Front 14

What is the effect of M1 and M3 activity on TRP channels?

Back 14

1. Activation--- generation of AP to stay awake

Front 15

What are the important dopamine-containing nuclei?

Back 15

1. VTA

2. vPAG

3. Increase activity during wakefulness

Front 16

What is the MOA of amphetamines?

Back 16

1. Block dopamine repute to increase extracellular dopamine

2. increases dopamine receptor activation

Front 17

How does dopamine increase arousal?

Back 17

1. Activation of D2

2. D2 inhibits Kv7 and activates TPR channels

Front 18

When is NE activation in the locus coeruleus?

Back 18

1. Higher when awake

2. Low during sleep

Front 19

How does NE maintain wakefulness?

Back 19

1. Increase activity of GPCRs, a1, a2, B1, and B2 receptors

2. Inhibit Kv7 and activate TRP

3. Inhibits please of GABA from VLPO

Front 20

How does NE inhibit the VLPO?

Back 20

1. a2 receptors inhibit GIRK activation

2. GAB release suppressed

Front 21

What does 5-HT induce?

Back 21

1. Quiet, relaxed awake state

Front 22

Where are histamine-containing neurons located?

Back 22

1. Tuberomammillary nucleus (TMN)

Front 23

How does histamine modulate wakefulness?

Back 23

1. H3 receptors sense histamine released by TMN to inhibit further release

2. TMN activity is increased--- cortical HA and arousal increased

Front 24

Where are orexin neurons located?

Back 24

1. Lateral hypothalamus

Front 25

What is the role of orexin? How does it work?

Back 25

1. Activation of arousal nuclei

2. Enhanced by fasting

3. Activates OxR1 and OxR2--- inhibition of Kv7 and activation of TRP

Front 26

What is the MOA of suvorexant?

Back 26

1. Blocks orexin

Front 27

How is orexin involved in narcolepsy and cataplexy?

Back 27

1. Low CSF levels of orexin is diagnostic

Front 28

What do NE neurons excite?

Back 28

1. TMN

2. Raphe nucleus

3. Basal forebrain

Front 29

What do HA neurons excite?

Back 29

1. TMN

2. LC

3. Raphe

4. Basal forebrain

Front 30

What do ACh neurons excite?

Back 30

1. Orexin via M3--- inhibition of Kv7 and activation of TRP

Front 31

What do 5-HT neurons inhibit?

Back 31

1. Basal forebrain

2. Orexin

Front 32

How does GABA induce sleep?

Back 32

1. VLPO releases galanin and GABA to inhibit lateral hypothalmus, raphe nucleus, LC, TMN, and LDT/PPT

Front 33

From where does the VLPO receive input?

Back 33

1. Retina

Front 34

What is the MOA of GABA B receptors?

Back 34

1. GPCR activation of GIRK--- hyperpolarization

Front 35

How does adenosine modulate sleep?

Back 35

1. Activation of A1 and A2 receptors induces sleep

2. Activate GIRK channels

3. Inhibition of ACh neurons

4. Activation of GABA in VLPO

Front 36

What is the MOA of caffeine?

Back 36

1. Blocks A2 receptors

Front 37

Where is the circadian system localized?

Back 37

1. Suprachiasmatic nucleus

Front 38

How is the SCN involved in circadian rhythms?

Back 38

1. Retinal ganglion cells transmit light signals to stimulate SCN

2. SCN neurons activate orexin and inhibit VLPO to promote awake state

Front 39

What are the components of the flip-flop model?

Back 39

1. VLPO-- sleep

2. TMN, 5-HT, and NE neurons

3. Each side inhibits the other--- activation of one must be stronger than the other

Front 40

What regulates the synthesis of melatonin?

Back 40

1. SCN--- senses light and darkness

2. MT1 attenuates alerting signal (sleep)

3. MT2 shifts SCN clock (sleep)

Front 41

What is the MOA of rozerem?

Back 41

1. Activates MT1 and MT2 to promote sleep

Front 42

What is stage 1 sleep?

Back 42

1. Transition from wakefulness to sleep

2. 5% of sleep

Front 43

What are stages 2 and 3 of sleep?

Back 43

1. Sleep spindles and K-complexes on EEG

2. Amplitude increases

3. Frequency slows

4. 40-60% of sleep time

Front 44

What is stage 4 sleep?

Back 44

1. Slow-wave sleep

2. Deepest sleep

3. 10-20% sleep

4. Occurs during 1/3 to 1/2 of sleep

Front 45

What is REM sleep?

Back 45

1. Dream sleep

2. 18-25% of sleep

3. Increases in duration throughout the night

4. Low-amplitude, high frequency activity

Front 46

What happens during NREM sleep?

Back 46

1. GABA neurons in VLPO inhibit RAS orexin, histamine, serotonin, NE, and dopamine

Front 47

What are the REM-on neurons?

Back 47

1. ACh in lDT/PPT

2. GABA/glycine neurons in ventromedial medulla

Front 48

What is the role of MCH in REM?

Back 48

1. Inhibit NE, 5-HT, and HA neurons

2. Inhibit REM-off neurons in vPAG/LPT

3. Master regulator of sleep

Front 49

What controls the transition from REM to NREM?

Back 49

1. REM-off in vPAG/LPT and REM-on in SLD