Modulatory and arousal systems

Question 1

What is the pathway of the specific primary visual pathway?

Answer 1

Retina -> thalamus -> primary visual cortex

Arrows represent sensory info

Question 2

Where are modulatory inputs found in the brain?

Answer 2

Brainstem & basal forebrain

Question 3

What is happening in the primary visual pathway when one is awake?

Answer 3

The thalamic cells are relaying sensory info to the cortex

Question 4

What is happening in the primary visual pathway when we are asleep?

Answer 4

Thalamic cells become insensitive to their sensory input.

This is due to withdrawal of modulatory input, so the thalamic cells start to fire bursts of APs in rhythmic, regular manner but the cortex is no longer receiving the sensory input from retina.

Question 5

Describe what the electroencephalogram looks like while (i) awake and (ii) asleep.

Answer 5

• Awake - desynchronised eeg - low amp, high freq
• Asleep - synchronised eeg - high amp, low freq

Question 6

Describe what happens to an EEG during the 4 stages of sleep, going from awake/relaxed to deep sleep

Answer 6

As you go down the stages into deeper sleep, the EEG shows the amplitude getting higher and the frequency lower.

The synchronisation also increases in the thalamus and cortex.

Question 7

Describe what happens in the brain and EEG during Rapid Eye Movement (REM) sleep

Answer 7

REM occurs following the ascent of the 4 stages of sleep.

The EEG looks desynchronised, so makes it look like you are awake (low amp, high freq) but really you are in paralysis.

There is an active ‘higher’ cortex, limbic and sympathetic NS -> suggests dreaming!

Question 8

How does the sleep cycle change over the night?

Answer 8

Over the night, the REM becomes longer and the non-REM (4 stages) becomes shallower and shorter.

Question 9

What are the two important centres of the cholinergic modulatory pathway, and what do they project to?

Answer 9

• Basal forebrain -> projects to neocortex and hippocampal complex
• Pontomesencephalic tegmentum -> projects to thalamus + basal ganglia

Question 10

What are the actions of the Acetycholine modulatory pathway?

Answer 10

• Desynchronises thalamic cells, maintains connection to outside world
• Increases response strength, selectivity and plasticity
• Keeps awake, attentive, increases cognition, learning, memory

Question 11

What happens in dysfunction of the acetylcholinergic modulatory pathway? Example? What drug is used to treat?

Answer 11

• Dysfunction -> cog decline, memory issues
• Eg. Alzheimer’s
• Treat with AChE inhibitor (Aricept)

Question 12

What are the actions of the norepinehprine / noradrenergic modulatory pathway?

Answer 12

• Similar to ACh
• Inc response amplitde + selectivity, inc plasticity
• Keep awake/vigilant, alert to novel stimuli, inc learning, memory and mood

Question 13

What does dysfunction of the norepinehprine / noradrenergic modulatory pathway lead to? How can it be treated?

Answer 13

• Dysfunction -> anxiety, depression
• Treated with NE (norepinephrine) reuptake inhibitors
• Treated with MAO inhibitors
• ^Drugs also boost analgesic effect down the spinal cord

Question 14

What is the norepinephrine modulation centre in the brain?

Answer 14

Locus coeruleus

Question 15

What are the dopaminergic modulatory pathways and where do they project to?

Answer 15

• Substantia nigra -> projects to basal ganglia
• Ventral tegmental area -> projects to frontal cortex, limbic, amygdala, nucleus accumbens

Question 16

What is the nucleus accumbens?

Answer 16

Pleasure centre

Question 17

Why is the substantia nigra pathway important in dopaminergic modulation? What does downregulation lead to and how is it treated?

Answer 17

The pathway facilitates voluntary movement by activating the “direct” basal ganglia pathway, and reduces suppression of movement by the “indirect” basal ganglia pathway.

Decreased activity -> Parkinson’s disease, treated with L-DOPA

Question 18

What is important about the ventral tegmental area in dopaminergic modulation? What does increased activity lead to and how is it treated?

Answer 18

Involved in reinforcement of behaviour, promoting behaviour that leads to reward.

Inc activity -> schizophrenia, amphetamines, treated with DA antagonists

Question 19

What is the consequence of giving dopaminergic drugs, in regards to (i) anti-parkinson’s, (ii) anti-psychotics

Answer 19

• Anti-parkinson’s (LDOPA) can result in increased psychotic behaviour
• Anti-psychotics (DA antagonists) can result in dyskinesia

Question 20

What is the histamine modulatory pathway centre and where does it project to?

Answer 20

Hypothalamus -> thalamus + cortex

Question 21

What is the role of the histamine modulatory pathway? What is a consequence of anti-histamines?

Answer 21

• Wakefullness, alertness
• Antihistamines result in drowsiness

Question 22

Where does the orexin modulatory pathway originate and project to?

Answer 22

From the hypothalamus to _~ everywhere

Question 23

What is the role of the orexin modulatory pathway? What does dysfunction lead to?

Answer 23

• Wakes you up
• Responds to nutritional status
• Linked to reward centres
• Awake + exploring, energy homeostasis

Dysfunction -> narcolepsy

Question 24

What is the sertonergic modulatory pathway centre and where does it project?

Answer 24

Raphe nuclei -> _~ everywhere

Question 25

What is the role of the serotonin modulatory pathway? What does dysfunction lead to?

Answer 25

• Quiet waking
• Appropriate responses to stress
• Mood

Dysfunction -> anxiety, depression - treated with SSRI, MAO inhibitors (also analgesic)

Question 26

How do the modulatory pathways discussed arouse us from sleep to being awake? Describe using locations and NTs

Answer 26

• Hypothalamus stimulated to release orexin + histamine
• activates brainstem (ARAS) -> releases serotonin, ACh, NE
• desynchronises eeg
• activates basal forebrain -> releases ACh
• increases response strength + selectivity

Question 27

A lesion in which part of the brain will prevent a person waking up ie. result in coma?

Answer 27

The brainstem (ascending reticular activating system) is crucial for waking up

Question 28

What happens to the modulatory systems in order for us to fall asleep? What does dysfunction of this lead to?

Answer 28

• VLPN of hypothalamus (GABA) acts as off switch
• projects to hypothalamus and brainstem and switches them off
• reduced wake-promoting activity, increased synchronisation
• drift off to sleep

Dysfunction -> insomnia

Question 29

What stimulates falling asleep (activates the VLPN/Hypothalamus GABAergic pathway)?

Answer 29

• Circadian rhythm (suprachiasmatic nucleus)
• Tiredness (eg build up of adenosine) (prevented by caffeine)
• Illness (inc immune by-products)

Question 30

What is going on in the brain during REM sleep?

Answer 30

The hypothalamus GABAergic signals are still active, which downplay the brainstem and hypothalamus NTs like in sleep. Except, cholingeric activity from brainstem switches on. On its own it can’t wake you up but can desynchronise EEG – allows cortex to process info.

This switches on basal forebrain, which switches on cells that project to higher cortical areas and limbic associated areas. These are active during dreaming. ALL meaningful activity, generated internally.

Cholinergic system also switches on pathway that suppresses skeletal muscle activity (apart from the eyes).

Question 31

When does one suffer narcolepsy?

Answer 31

Due to a lesion present in the orexin modulatory system, disrupts sleep-wake cycle. Waking dreamlike episodes (hallucinations) and cataplexy (REM-like paralysis) - brought on by strong emotion, on the floor awake but paralysed.