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The Nervous System & Respiratory Diseases > Neuromodulators (L4-5) > Flashcards

Neuromodulators (L4-5) Flashcards

1
Q

What technique associated with Human/Animal imaging can be used to study neuromodulators?

A

PET studies of receptor binding.

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2
Q

How can you study neuromodulators in whole animals?

A
  • inject a drug and assess effect on behaviour
  • inject a drug and record neuronal activity
  • genetically modified animals e.g. lacking a receptor subtype
  • lesion regions – effects on behaviour
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3
Q

How can you study neuromodulators in vitro?

A

LTP, single cell activity, network activity.

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4
Q

Neuromodulator transmitters should not be regarded as purely excitatory or inhibitory. Why?

A
  • Their exact action depends on receptors, context, levels.

- On the same cell, they can be either excitatory or inhibitory.

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5
Q

With a few exceptions, what type of receptor do neuromodulators act upon? This being the main reason neuromodulators can both excite and inhibit.

A

Metabotropic.

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6
Q

What are pyramidal cells?

A

The principle excitatory cells of the cortex.

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7
Q

Name the 3 parts that make up a pyramidal cell.

A
  • Soma
  • Apical dendrites
  • Basal dendrites
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8
Q

Define an Interneuron.

A

An interneuron is a neuron that forms a connection between other neurons. Interneurons are neither motor nor sensory.

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9
Q

Where are monoamines produced?

A

In the nuclei of the brainstem.

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10
Q

Dopamine neurons are present in which 2 regions of the brainstem?

A
  • A10 = Ventral tegmental area

- A9 = Substantia nigra

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11
Q

True of false? Overall there are a large number of DA neurons in the brain.

A

False. Overall there are a small number of DA neurons in the brain, 1 million/10 billion.

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12
Q

Name the 3 main Dopamine pathways.

A
  • Mesocortical pathway
  • Mesolimbic pathway
  • Nigrostriatal pathway
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13
Q

Describe the Mesocortical pathway.

A

Ventral tegmental area to prefrontal cortex. PFC important for higher cognitive functions such as motivation, planning, attention and working memory.

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14
Q

Describe the Mesolimbic pathway.

A

Ventral tegmental area to amygdala, hippocampus and frontal cortex. Thought to be involved in reward, euphoria induced by drugs.

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15
Q

Describe the Nigrostriatal pathway.

A

Neurons in substantia nigra mainly project to dorsal striatum. Part of the extrapyramidal motor system involved in the initiation and control of movement.

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16
Q

Ventral tegmental area neurons fire in two modes. What are they and what level of Dopamine do they release?

A

Tonic - Low levels

Phasic - High levels

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17
Q

What is tonic firing of DA?

A

Background level of dopamine release.

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18
Q

True or false? DA (and NA) exhibit an inverted “U”shaped function.

A

True.

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19
Q

Describe the synthesis of DA from precursor to DA.

A

Precursor = Tyrosine
Tyrosine + Tyrosine Hydroxylase = DOPA
DOPA + DOPA decarboxylase = DA

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20
Q

Which 2 enzymes breakdown DA?

A

Monoamine oxidase & COMT.

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21
Q

What does the Dopamine Transporter (DAT) do and where is it found?

A

It limits DA transmission and is only found on DA terminals.

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22
Q

How does the Dopamine transporter work?

A

Active transport by an Na/K ATPase pump which pushes through a DA molecule in every cycle.

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23
Q

Name the D1 like receptors.

A
  • D1

- D5

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24
Q

Name the D2 like receptors.

A
  • D2
  • D3
  • D4
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25
Q

True or false. Dopamine receptors are all metabotropic G-protein coupled receptors.

A

True.

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26
Q

D1-like receptors couple to Gs and do what?

A

Stimulate adenylate cyclase and therefore increase cAMP.

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27
Q

D2-like receptors couple to Gi and do what?

A

Inhibit adenylate cyclase and therefore decrease cAMP.

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28
Q

How many membrane alpha helices do Dopamine receptors have?

A

7.

29
Q

Where on the neuron are DA receptors present?

A

Present on soma, dendrites, and nerve terminal.

30
Q

Stimulation of DA receptors have different effects depending on the receptor location. Presynaptic autoreceptors regulate what?

A

Release of DA from terminals.

31
Q

Which disease stems from the loss of dopamine neurons in the substantia nigra?

A

Parkinson’s disease.

32
Q

How would you cause animals to display symptoms of Parkinson’s disease, what does this do to the animal and how would you reverse the process?

A

Inject 6-OHDA which causes loss of dopamine neurons in the substantia nigra and VTA.
Lesioned animals shows reduced learning deficits and LTP.
LTP and learning deficits reversed by L-DOPA treatment.

33
Q

Define Long Term Potentiation (LTP).

A

Long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously.

34
Q

True or false? Dopamine modulates the synaptic plasticity (LTP) thought to underlie learning and memory.

A

True.

35
Q

Having Parkinson’s disease does what to the size of the hippocampus?

A

Reduces its size.

36
Q

Coacaine and amphetamine work by blocking which transporters?

A

The monoamine transporters.

37
Q

Which drug, cocaine or amphetamine also causes further dopamine to be released?

A

Amphetamine.

38
Q

What is the overall effect of amphetamine and cocaine on the synaptic cleft?

A

Increased dopamine and noradrenaline concentration in the cleft.

39
Q

Amphetamine causes weak inhibition of __________ _________ so prevents degradation of DA leaving free DA in terminals.

A

Monoamine oxidase.

40
Q

List the roles of Serotonin (5-HT) in the body?

A
  • Regulating food intake
  • Learning and Memory
  • Sleep-wake cycle
  • Aggression
41
Q

The 5-HT neurones arise from the _____ nucleus in the brainstem.

A

Raphe.

42
Q

Describe the synthesis of 5-HT from precursor to 5-HT.

A

Precursor = L-Tryptophan
L-Tryptophan + Tryptophan Hydroxylase = 5-HTP
5-HTP + L-amino acid Decarboxylase = 5-HT

43
Q

What type of vesicles is Serotonin stored in?

A

Large dense core vesicles.

44
Q

Name the 5-HT re-uptake transporter.

A

The Serotonin Transporter (SERT)

45
Q

What is 5-HT broken down by?

A

Monoamine oxidase.

46
Q

How many subtypes of Serotonin are there?

A

14.

47
Q

Which 5-HT receptor subtypes are G-protein linked receptors?

A

5-HT 1,2,4,5,6,7.

48
Q

Which 5-HT receptor subtype is ionotropic?

A

5-HT 3.

49
Q

Which 5-HT receptor subtypes are important in learning and memory?

A

5-HT1A, 5-HT4 and 5-HT6.

50
Q

Name the diseases of Serotonin dysfunction.

A
  • Depression
  • Anxiety disorders
  • Bipolar disorder
  • Schizophrenia
  • Obsessive compulsive disorder
51
Q

Name some major symptoms of depression.

A
  • depressed mood
  • apathy
  • weight changes
  • sleep disturbances
  • agitation
  • fatigue
  • worthlessness
  • executive dyfunction
  • suicidal ideation
52
Q

What is the most widely used drug to treat depression and how does it work?

A

Prozac - Selective and potent inhibitor of SERT.

53
Q

List the roles of noradrenaline (NA).

A
  • Learning and memory
  • Sensory processing
  • Attention
54
Q

Where do NA neurons arise from?

A

Locus Coeruleus.

55
Q

Describe the firing of Locus Coeruleus neurons whilst awake and in different stages of sleep.

A
  • Highest firing when awake.
  • Lower during slow-wave sleep.
  • Virtually silent during REM or paradoxical sleep.
56
Q

Noradrenaline has the same synthesis pathway as DA apart from the last stage where DA becomes NA due to the activity of what enzyme?

A

Dopamine Hydroxylase.

57
Q

True or false? NA transporter works in the same way as DA transporter.

A

True

58
Q

Name the adrenergic receptor subtypes and what happens when each is activated.

A

a1 - adrenoceptors activate phosopholipase C, producing IP3 and DAG.
a2 - inhibit adenylate cyclase and decrease cAMP.
β1, β2, β3 - all stimulate adenylate cyclase and increase cAMP.

59
Q

Name the transporter that transports vesicles containing monoamines to the presynaptic membranes.

A

VMAT.

60
Q

What is ADHD characterised by?

A
  • inattention
  • hyperactivity
  • impulsivity
61
Q

What are the treatments for ADHD? And what simply do they do?

A

Psychostimulants (Ritalin) and guanfacine. Increase DA and NA levels.

62
Q

ADHD is a genetic polymorphism of what?

A

Dopamine β Hydroxylase.

63
Q

What effect of ADHD is used as a diagnostic tool?

A

Decreased NA synthesis.

64
Q

What 2 chemicals react to form Acetlycholine? And what enzyme catalyses the reaction?

A

Acetyl CoA+Choline. Choline Acetyltransferase

ChAT

65
Q

What process does Co-enzyme A arise from?

A

Glucose metabolism.

66
Q

No re-uptake of Ach occurs in the synaptic cleft. Instead it is broken down into its constituent parts. Which enzyme catalyses the brekdown?

A

Acetylcholinesterase (AChE).

67
Q

Name the 2 main receptor subtypes of Ach receptors. Are they ionotropic or metabotropic? Also name the subtypes of each.

A

Nicotinic - Ionotropic - a7 and a4β4

Muscarinic - Metabotropic - M1- M5

68
Q

What is Alzheimers disease?

A

Form of dementia characterised by degeneration of the basal forebrain cholinergic neurons.

69
Q

What are the symptoms of Alzheimers disease?

A
  • Difficulty maintaining and sustaining attention
  • Memory loss
  • Mood changes - depression, irritability
  • Psychosis - hallucinations, paranoid delusions
  • Psychomotor - wandering, pacing
  • Sleep-wake disturbances

The Nervous System & Respiratory Diseases (15 decks)

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