Locus Coeruleus Flashcards

1
Q

TRUE or FALSE: the pre-BotC is necessary to keep us alive

A

TRUE

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2
Q

opiate vs opoid

A

opiate is natural; opioid is synthetic or natural

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3
Q

Which type of opioid receptor is most sensitive to analgesic effects of opiods?

A

mu-receptors

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4
Q

Why is the pre-BotC important for life?

A

rhythmogenic inspiratory center that results in rhythmic contraction of inspiratory muscles needed to ventilate the lungs

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5
Q

What does the locus coeruleus play a cruicial role in?

A

causing death in association with the effect of opioids on the activity of its neurons

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6
Q

TRUE or FALSE: pre-BotC is crucial for death and LC is crucial for life

A

FALSE: preBotC for life, LC for death

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7
Q

Explain how the LC and pre-BotC communicate with each other.

A
  • pre-BotC neuron bursting evokes rhythmic inspiratory-related spike discharge or trains of IPSPs in LC neurons
  • LC neurons release NTs inside pre-BotC can modultae pre-BotC bursting
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8
Q

Where are the pre-BotC and LC located?

A
  • pre-BotC: ventrolateral brainstem
  • LC: dorsal surface of brainstem (next to 4th ventricle)
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9
Q

function of pre-BotC vs LC?

A
  • pre-BotC: generate inspiratory rhythm
  • LC: tonic or bursting vs. phasic neuron activity
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10
Q

TRUE or FALSE: the LC only innervates the hypothalamus and the thalamus.

A

FALSE: LC innervates almost all brain structures

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11
Q

Which NT does the LC release?

A

NA

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12
Q

Effect of exogenous opioids on LC neurons

A

dependence; suicidal ideation; overdose

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13
Q

How does overdosing on opioids kill humans?

A

abolish preBotC rhythm that drives breathing movements

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14
Q

What does locus coeruleus mean in english?

A

sky in the brain

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15
Q

TRUE or FALSE: there are very few LC neurons.

A

TRUE

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16
Q

What did the injkection of the green fluorescent dye Fluo-4 into the LC slice reveal?

A

LC neurons have large soma diameters (dye did not differentiate between astrocytes and neurons)

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17
Q

How do you differentiate between neurons and astrocytes in the LC, when staining?

A
  • stain TH antibody found in neurons red
  • stain S-100B protein found in astrocytes green
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18
Q

What is ‘tonic’ spiking of a neurons?

A

non-phasic spontaneous discharge of single Na+ APs (spikes)

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19
Q

What is bursting of neurons?

A

slow rhythmic depolarizations, caused by prolonged excitatory synaptic inputs with activation of intrinsic ion channels

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20
Q

via recording in the reticulo-thalamic neuron, it was revealed that wakefulness is associated with bursting or tonic spiking?

A

tonic spiking

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21
Q

via recording in the reticulo-thalamic neuron, it was revealed that sleep is associated with bursting or tonic spiking?

A

bursting

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22
Q

At low attention, do we have spiking or bursting?

A

spiking

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23
Q

At high attention, do we have spiking or bursting?

A

bursting

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24
Q

Which is associated with good and poor performance, between spiking and bursting

A
  • bursting = good performance
  • spiking = poor performance
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25
Q

What type of drug is clonidine?

A

alpha 2 NA receptor agonist

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26
Q

when clonidine is administered:
a) spiking becomes bursting
b) bursting becomes spiking

A

a) spiking becomes bursting

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27
Q

What is clonidine used to treat? What is the mechanism?

A
  • ADHD
  • its action on LC can increase performance/attention (bursting)
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28
Q

neuronal firing patterns determine behaviour. How is this demonstrated in the LC?

A
  • poor performance associated with spiking and low attention
  • good performance associated with bursting and high attention
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29
Q

In what manner is NA released from the LC?

A

pulsatile

30
Q

Which receptors does NA act on? Which ones are excitatory / inhibitory?

A
  • alpha 1, beta 1 = excitatory
  • alpha 2 = inhibitory
31
Q

What is the effect of noradrenaline on the squirrel monkey auditory cortex?

A

inhibitory (decreased duration of spiking)

32
Q

Describe the inhibitory effect of NE on the squirrel monkey auditory cortex.

A
  • inhibit irregular firing
  • decrease spiking amplitude
  • decrease spiking duration
33
Q

TRUE or FALSE: LC is only involved in the modulation of sensation of pain.

A

FALSE: senses of pain, audition, vision, gustation, olfaction

34
Q

TRUE or FALSE: LC both projects and and receives info.

A

TRUE: receives info about internal state of the body (interoception) via brainstem nuclei

35
Q

What is interoception? which 2 nuclei are involved?

A

visceral afferents from bladder, bowel, heart, gut to LC via Barrington’s nucleus and Paragigantocellularis

36
Q

LC has a modular organization. What does this mean?

A

it has a preferred location of subpopulations of its neurons with different features.

37
Q

In terms of cell morphology in the LC, where are noradrenaline-positive (NE+) fusiform neurons?

A

dorsal

38
Q

In terms of cell morphology in the LC, where are noradrenaline-positive (NE+) multipolar neurons?

A

ventral

39
Q

TRUE or FALSE: all LC neurons contain NE while thy also express another neurotransmitter (cotransmitters)

A

TRUE

40
Q

WHat are the subsets of LC neurons that co-release peptides?

A
  • NE+/galanin+
  • NE+/NPY+
41
Q

What are the subsets of LC neurons that express different subtypes of noradrenaline receptors?

A
  • NE+/AR-alpha-1+
  • NE+/AR-alpha-2+
42
Q

In terms of projection target, where are Th-projecting LC neurons found?

A

posterior part of the dorsal LC

43
Q

In terms of projection target, where are Hi-projecting LC neurons found?

A

medial and anterior part of the dorsal LC

44
Q

In terms of projection target, where are Cb-projecting LC neurons found?

A

ventral part of LC

45
Q

TRUE or FALSE: the hypothalamic nuclei has both afferents and efferents to the LC

A

FALSE: the amygdala has both afferents and efferents to the LC

46
Q

Draw the afferent inputs to LC

A

slide 10

47
Q

List the afferent inputs to the LC

A
  • preBotC
  • preoptic area
  • nucleus paragigantocellularis
  • cortex orbito-frontal and anterior cingulate
  • amygdala
  • hypothalamic nuclei
  • dorsal and median raphe
48
Q

which neurotransmitter is released from the preoptic area to the LC?

A

GABAa

49
Q

which neurotransmitter is released from the nucleus paragigantocellularis to the LC?

A

glutamate

50
Q

which neurotransmitter is released from the cortex orbito-frontal and anterier cingulate to the LC?

A

glutamate

51
Q

which neurotransmitter is released from the amygdala to the LC?

A

glutamate and CRF

52
Q

which neurotransmitter is released from the hypothalamic nuclei to the LC?

A

hypocretin and orexin

53
Q

which neurotransmitter is released from the dorsal and median raphe to the LC?

A

5-HT

54
Q

NA can be released via an axon collateral on the same, or neighbouring, LC neurons or on astrocytes to act on alpha 1 or alpha 2 ‘autoreceptors’. what does this imply about LC neurons, during ENHANCED ACTIVITY?

A

LC neurons also release NA next to neighbouring LC neurons and astrocytes and this MIGHT CHANGE THEIR ACTIVITES (slide 10)

55
Q

Using optogenetic activation of LC neurons, compare tonic and phasic activity in terms of which:

  • induce wake from sleep
  • increase periods of wakefulness
  • increase locomotion
  • induce anxiety-like behaviour
  • decrease locomotion
A
  • both induce wake from sleep
  • both increase periods of wakefulness
  • tonic increases locomotion
  • tonic induces anxiety-like behaviour
  • PHASIC decrease locomotion
56
Q

What is the difference between tonic and phasic spike discharge? draw them on a graph

A
  • tonic = evoked by light pulses with regular pattern
  • phasic = evoked by shorter sequence of briefer light pulses at HIGHER RATE

(slide 11)

57
Q

What is the difference between ChAT+ and GABA+ LC output sites?

A

ChAT+ neuron
- express alpha1 and beta1 receptors that are both EXCITATORY
- NA released from LC onto these receptors –> excitation of ChAT+ neuron –> discharge more intensely –> release more ACh into cortex –> promote arousal

GABA+ neuron
- express INHIBITORY alpha2 receptor
- NA released from LC onto these receptors –> DEPRESSION of GABA+ neuron activity –> discharge less intensely –> release GABA into cortex –> inhibit arousal/promote sleep

58
Q

How does morphine application change AP firing? (before and after)

A
  • before morphine: unsynchronous tonic firing
  • after morphine: synchronous slow bursting
59
Q

TRUE or FALSE: alpha-2 agonists and mu-opioid agonists evoke similar discharge behaviour

A

TRUE

60
Q

What kind of discharge behaviour do alpha-2 agonists and mu-opioid agonists evoke?

A

slow, synchronous bursting

61
Q

TRUE or FALSE: the tonic spiking in LC neurons evoked by morphine helps alleviate pain

A

FALSE: slow, synchronous bursting alleviate pain

62
Q

Why do clonidine and opioids exert the same transforming effect on LC neuron spiking?

A
  • their receptors are both coupled to the same second-messenger signaling pathway (GPCR)
  • both cause hyperpolarization of the cell due to K+ efflux via GIRK channels
63
Q

TRUE or FALSE: activation of GIRK channels causes depolarization

A

FALSE: hyperpolarization via K+ efflux

64
Q

What is the paradox of in vivo vs in vitro administration of opioids in the LC neurons?

A
  • in vivo: opioids transform tonic spiking into synchronous bursting (NO INHIBITION)
  • in vitro: opioids cause hyperpolarization and spike blockade (INHIBITION)
65
Q

How does NA affect K+ currents? Same or different than opioid effect?

A

K+ outward current (like opioids)

66
Q

What is metenkephalin? How does it affect K+ current

A
  • opioid agonist
  • induce K+ outward current
67
Q

What is normorphine? How does it affect K+ current

A

CHECK GROUP CHAT

68
Q

How does local injection of kynurenic acid into LC affect firing rate during steady-state effect of morphine? What does this indicate about morphine-evoked pattern transformation?

A
  • morphine: tonic spiking –> bursting
  • kynurenic acid = iGluR (ionotropic glutamate receptor) blocker
  • kynurenic acid: bursting –> tonic spiking
  • indication: morphine-evoked pattern transformation depends on iGLuR in the LC
69
Q

What does the morphine-evoked pattern transformation depend on within the LC?

A

iGluR

70
Q

TRUE or FALSE: LC has intrinsic capability to transform its burst pattern only in vivo.

A

FALSE: also in vitro and in newborns (as shown by iGluR involvement experiment)

71
Q

What kind of recording can be used to pharmacologically analyze the LC network?

A

suction electrode recording of local field potential (LFP) in the LC

72
Q

TRUE or FALSE: left and right LC fire synchronously

A

FALSE: left and right LC do NOT fire synchronously