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Neuroscience Y2S2 > Neurobiology of Disease 6 > Flashcards

Neurobiology of Disease 6 Flashcards

1
Q

Is epilepsy thought to be monogenetic or polygenetic, where there is a genetic cause? (1)

A

Can be either

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2
Q

Define ‘epilepsy’. (2)

A

A pathologic and enduring tendency to have recurrent seizures

and the neurobiological, cognitive, psychological, and social consequences.

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3
Q

Give a structural cause of epilepsy. (1)

A

Malformations of development

(ie, where brain development results in a malformation)

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4
Q

Give four acquired causes of epilepsy. (4)

A
  • Trauma
  • Infection
  • Tumour
  • Stroke
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5
Q

When are structural/malformation causes of epilepsy most likely to present? (1)

A

Early childhood

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6
Q

When might polygenetic causes of epilepsy present? (1)

A

Later in life

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7
Q

Define ‘seizure’. (1)

A

A transient occurrence of signs and/or symptoms due to abnormal, excessive, or synchronous neuronal activity in the brain.

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8
Q

True or false? Explain your answer if appropriate. (1)

In some circumstances, seizures can be ‘silent’, and can occur without the person having signs or symptoms.

A

False - a seizure cannot occur without the person having symptoms, however might occur without any external signs

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9
Q

What neurological condition is described below? (1)

This condition arises due to abnormal neuronal firing in a particular brain network.

A

Seizure

(or epilepsy)

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10
Q

Give seven things/factors that differ between different seizure types. (7)

A
  • Brain network involved
  • Whether consciousness is altered
  • Signs and symptoms
  • EEG signature
  • Original cause of abnormal firing
  • Response to drug therapy
  • Prognosis (final outcome)
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11
Q

Give three ways in which seizures can be classifies. (3)

A
  • Focal or generalised onset
  • Impaired awareness or maintained awareness
  • Motor or non-motor onset
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12
Q

How is a generalised seizure defined? (1)

A

Originating at some point within, and rapidly engaging, bilaterally distributed networks

(starts simultaneously in both hemispheres)

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13
Q

How is a focal seizure defined? (1)

A

Seizure starts in a specific focus or network limited to one hemisphere, and then spreads (can spread throughout both hemispheres)

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14
Q

Is generalised epilepsy more likely to be due to genetics or brain lesions? (1)

A

Genetics - multiple mutations each conferring small risk

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15
Q

Name three specific types of generalised seizures. (1)

A

Typical absence seizure

Myoclonic

Tonic-clonic

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16
Q

When do absence seizures usually begin? (1)

A

Childhood

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17
Q

Describe (give three features of) an absence seizure. (3)

A
  • Frequent brief attack (1-30secs)
  • With sudden loss and return of consciousness
  • And some involuntary movements
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18
Q

Describe the aura and post-ictal state in absence seizures. (2)

A

No aura

No post-ictal state

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19
Q

Describe a myoclonic seizure. (2)

A

Sudden, brief, shock-like muscle contractions

Which are usually bilateral in the arms

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20
Q

Give three things that can precipitate/bring on myoclonic seizures. (3)

A
  • Mornings (seizures worse in mornings)
  • Sleep deprivation
  • Alcohol
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21
Q

Describe the onset, tonic, clonic, and post-ictal phases of a tonic-clonic seizure. (4)

A

ONSET
- Sudden (commonly a gasp, followed by a fall)

TONIC
- stiffness (often with cyanosis)

CLONIC
- jerky

POST-ICTAL
- Significant drowsiness

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22
Q

As well as the classical stiffness and muscle jerks, give three other things that may happen during a tonic-clonic seizure. (3)

Give two symptoms which may occur in the post-ictal period. (2)

A
  • Tongue biting
  • Incontinence
  • Noisy breathing

POST-ICTAL:

  • Headache
  • Muscle pain
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23
Q

Describe the typical EEG pattern seen in an absence seizure. (2)

A

3Hz

spike and wave pattern

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24
Q

Why are absence seizures described as an ‘electroclinical syndrome’? (1)

A

Features both clinical symptoms and a typical EEG pattern

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25
Q

Are atonic seizures usually generalised or focal seizures? (1)

A

Usually generalised

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26
Q

Describe an atonic seizure. (2)

A

Sudden loss of muscle tone

Children often fall to the floor

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27
Q

Describe the duration and recovery of an atonic seizure. (2)

A
  • Brief duration
  • Quick recovery
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28
Q

Why are atonic seizures so dangerous? (2)

A

They often occur in children

and falling to the floor can cause serious injuries (including to the head)

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29
Q

What is it called when a seizure starts in one hemisphere and propagates to include the opposite hemisphere? (1)

A

Secondary generalised seizure

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30
Q

How do the symptoms of a secondary generalised seizure change throughout the duration of the seizure? (1)

A

The symptoms evolve to reflect the brain regions involved as the seizure propagates.

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31
Q

What is the difference between a partial seizure and a focal seizure? (1)

A

Partial is old terminology and focal is new terminology

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32
Q

What is the most common type of focal epilepsy? (1)

A

Temporal lobe epilepsy

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33
Q

Give three symptoms experienced during the warning (aura) phase of a temporal lobe seizure. (3)

A
  • Epigastric rising sensation
  • Olfactory and gustatory cues
  • Deja vu
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34
Q

True or false? Explain your answer if appropriate. (1)

Temporal lobe seizures usually do not feature a post-ictal phase.

A

False - they do

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34
Q

Give five symptoms/features commonly seen in a temporal lobe seizure. (5)

A
  • Loss of awareness
  • Arrest reaction
  • Blank stare
  • Oral automatisms (lip-smacking)
  • Manual automatisms
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35
Q

True or false? Explain your answer if appropriate. (1)

Seizures are a phenomenon unique to mammals.

A

False - it has been suggested that even invertebrate organisms such as C.elegans, Drosophila, and zebrafish are able to show epileptic activity.

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36
Q

Give an advantage of using non-human, and potentially invertebrate models to investigate seizures. (1)

A

Wider range of studies can be carried out with less ethical considerations.

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37
Q

Give three techniques/experimental set-ups that are often used in experiments investigating seizures. (3)

A
  • Hippocampal slices exposed to acute seizure-provoking stimuli
  • Animals with induced CNS injury causing seizures
  • Rodent genetic models
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38
Q

Give three general types of stimuli that can be used to induce seizures in hippocampal slices. (3)

A
  • Electrical stimulation
  • Bath medium
  • Drugs
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39
Q

Give two alterations to the bath medium that can be used to induce seizures in hippocampal slices. (2)

A
  • Low magnesium
  • Low calcium
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40
Q

Give 2 drugs (and what classes they are) which can be used to induce seizures in hippocampal slices. (2)

A

4-aminopyridine (potassium channel blocker)

Bicuculline (GABA blocker)

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41
Q

What is meant by measuring ‘local field potentials (LFP)’ when studying seizures? (1)

A

Using micro EEGs to record summed synaptic activity from thousands of neurones

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42
Q

What is meant by measuring ‘spikes’ when studying seizures? (1)

A

A measure of a single neurone firing (otherwise known as an action potential)

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43
Q

What is an inter-ictal spike, when referring to seizures and seizure activity in the brain? (1)

A

200ms event which occurs in between seizures, and is indicative of an area prone to seizures

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44
Q

Give the four stages of focal seizure activity on a neuronal/electrophysiological level. (4)

A
  • Initiation
  • Synchronisation
  • Propagation
  • Termination
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45
Q

Give three advantages of using hippocampal slice experiments to investigate seizure activity. (3)

A
  • Realistic epileptic discharges can be created
  • Can obtain very detailed neurophysiology and neuropharmacology measurements
  • More humane than using animals
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46
Q

Give three disadvantages of using hippocampal slice experiments to investigate seizure activity. (3)

A
  • It is a reduced model, and not all network connections are present
  • It can model acute seizures but not recurrent seizures
  • Usually, non-physiological triggers are needed
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47
Q

Give four aspects of the experimental set-up/design of hippocampal slice studies that may affect the results seen. (4)

A
  • Tissue from young vs old rodents
  • Whether GABAergic transmission in the brain slice is functional
  • Sometimes, an electrical stimulus is required to kick-start seizure activity - was this required?
  • What is the extracellular potassium concentration?
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48
Q

Complete the passage relating to hippocampal slice studies to investigate epilepsy and seizures. (6)

Hippocampal slice studies have highlighted the fact that epileptiform discharges may be due to range of different effects , including:

a) ………………………, which is a property primarily of ion channels

b) Synaptic changes (particularly those synapses involving …………………… and ………………………..)

c) Other cells present in the brain, such as ……………………..

d) Non-synaptic effects, such as ………………………… ions, electrical field effects, and ………………….. junctions

A

Neuronal bursting

glutamate

GABA

Glial cells

extracellular

gap

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49
Q

True or false? Explain your answer if appropriate. (1)

For a focal seizure to occur, both ‘epileptic neurones’ and ‘epileptic networks’ are needed.

A

True

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50
Q

Give three features of an epileptic network in the brain needed for synchrony. (3)

A
  • Divergent connections (one neurone connecting with many others)
  • Effective synapses
  • Minimum aggregate of neurones in a highly-connected network
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51
Q

Give four molecular/cellular events which occur during the initiation phase of a focal seizure. (4)

A
  • High frequency oscillations
  • Bursting of excitatory neurones
  • Overcoming of inhibition
  • Micro-seizures coalescing to trigger the main event
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52
Q

Complete the sentence relating to synchronisation of neurones during a focal seizure. (4)

There must be both ……………………. and ……………………. events acting on neuronal networks, and these events can be ……………………… or …………………………

A

Local

long-range

Synaptic

Non-synaptic

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53
Q

Give three non-synaptic events which may occur in order to produce synchronisation of neurones and neuronal networks during a focal seizure. (3)

A
  • Gap junctions
  • Field events
  • Micro-environment changes (eg. K concentration)
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54
Q

Give six molecular/cellular events which may occur during or lead to termination of a focal seizure. (6)

A
  • Synaptic inhibition
  • Depolarisation block
  • Depletion of synaptic components (eg. vesicles, ATP, and NTs)
  • Intracellular acidification
  • Hyperpolarisation due to K channels
  • Effects of neuromodulators
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55
Q

Give three examples of neuromodulators which may play a role in termination of focal seizures. (3)

A
  • Adenosine
  • Opioids
  • Endocannabinoids
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56
Q

Complete the sentence relating to generalised seizures. (3)

Generalised seizures show many of the same mechanisms as focal seizures, however generalised seizures are predominantly thought to be a disruption in normal communication between the ………………. and the ……………..
This network is called the ……………………… loop.

A

Cortex

Thalamus

Corticothalamic

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57
Q

Briefly describe how a generalised seizure may propagate and cause loss of consciousness. (3)

Name the various networks and brain areas involved.

A

Hyperexcitable bursting neurones in sensorimotor cortex

Rapid propagation to corticothalamic networks

Leading to spike and wave patterns within corticothalamic networks, leading to downregulation of consciousness mechanisms

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58
Q

Name a drug which might be particularly effective in generalised seizures and describe why it might be effective. (2)

A

Ethosuximide

Because it acts on the thalamus, which is implicated in generalised seizures.

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59
Q

Describe what is meant by epileptogenesis. (1)

A

The process by which a brain network that was previously normal is functionally altered toward increased seizure susceptibility.

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60
Q

Give five factors (either physiological or in experimental conditions) which can lead to epileptogenesis. (5)

A
  • Head trauma
  • Stroke
  • Drugs
  • Electrical activity (inducing a prolonged seizure)
  • Cortical iron implantation
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61
Q

Describe the status epilepticus animal model of epileptogenesis. (1)

A

Induce a very long seizure but rescue animal before death

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62
Q

How can febrile seizures in children lead to epilepsy? (2)

A

If seizure is long

can lead to temporal lobe scarring and focal epilepsy

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63
Q

Give two drugs that can be used to induce status epilepticus in animal models. (2)

A

Pilocarpine

Kainate

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64
Q

In addition to using drugs, give another method of inducing status epilepticus in animal models. (1)

A

Electrical stimulation

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65
Q

Give three types of animal models used to investigate epileptogenesis. (3)

A
  • Status epilepticus
  • Injury (head trauma / stroke / cortical iron implantation)
  • Kindling
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66
Q

Briefly describe the kindling method of modelling epileptogenesis in animals. (1)

A

Electrode inserted into hippocampus or amygdala, and repeat sub-convulsive stimuli applied

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67
Q

For which experimental use is a kindling animal model of epileptogenesis particularly useful? (1)

A

Testing drugs for focal onset seizures

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68
Q

Describe how the brain changes throughout the early stages of kindling to the late stages (overkindling) when producing an animal model of epileptogenesis. (2)

A

Early stages increases inhibition

Over-kindling (100+ stimuli) causes cell loss (potentially of inhibitory interneurones), abnormal neuronal sprouting, and spontaneous seizures.

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69
Q

As well as spontaneous seizures, give two cognitive deficits that may be experienced in rodents due to the kindling method of modelling epileptogenesis. (2)

A

Memory deficits

Spatial deficits

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70
Q

True or false? Explain your answer if appropriate. (1)

Kindling, an animal model of epileptogenesis, can be reversed, and can only be performed in rodents.

A

False - it is permanent, and can occur in various species, including primates

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71
Q

Give four changes that are seen in a rodent model of epileptogenesis, once the rodent is in the ‘fully kindled state’. (4)

A
  • Enhanced seizure susceptibility
  • Behavioural and cognitive alterations
  • Physiological and neurochemical alterations
  • Discrete histological alterations (eg. neurodegeneration and sprouting)
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72
Q

Give six structural/gross changes that are thought to occur in epileptogenesis. (6)

A
  • Cell loss (inhibitory interneurones, leading to disinhibited circuits)
  • Axonal sprouting (leading to extra excitatory circuits)
  • Neurogenesis
  • Gliosis
  • Neuroinflammation
  • BBB breakdown
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73
Q

Give four molecular changes that are thought to occur in epileptogenesis. (4)

A
  • Changes to ion channels
  • Changes to receptors
  • Changes to neurotransmitter transporters
  • Changes to neuromodulators (such as peptides and endocannabinoids)
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74
Q

Give five types of ion channels which may be altered during epileptogenesis. (5)

What is the name for when an ion channel is changed due to injury etc? (1)

A

Na

K

Ca

Cl

HCO3

Acquired channelopathies

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75
Q

Name four receptors which might be altered during epileptogenesis. (4)

A

GABA

AMPA

NMDA

ACh

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76
Q

Give two functional changes that are thought to occur in epileptogenesis. (2)

A
  • Gap junctions
  • Glial cells (eg. buffering of extracellular environment)
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77
Q

Give four general considerations to be taken into account when treating epilepsy. (4)

A
  • Is the diagnosis correct?
  • Matching of drug treatment to syndrome and lifestyle
  • General lifestyle advice
  • Identifying who might be a surgical candidate
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78
Q

Give four lifestyle aspects that patients may need to be advised about in epilepsy. (4)

A
  • Alcohol
  • Drugs
  • Late nights
  • Driving
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79
Q

Give a lifestyle consideration to be taken into account when prescribing drugs for epilepsy. (1)

A

Valproate cannot be used in pregnancy

80
Q

Give two animal models of acute seizures which can be used to screen for anti-epileptic drugs. (2)

A

Maximal electroshock seizure (MES) test

Subcutaneous pentylenetetrazole (PTZ) seizure test

81
Q

Describe the maximal electroshock seizure (MES) test for animal models of testing epileptic medications in acute seizures. (3)

A

Brief application of an electric stimulus via transcorneal or transauricular electrodes

Endpoint is generalised tonic-clonic seizure

Can then test for anti-seizure activity against GTCS

82
Q

Give an advantage and disadvantage of the maximal electroshock seizure (MES) test for animal models of testing epileptic medications in acute seizures. (2)

A

ADVANTAGE:

  • Led to the discovery of phenytoin

DISADVANTAGE:

  • Levetiracetam not effective in this model but is effective in clinical situations
83
Q

Describe the subcutaneous pentylenetetrazole (PTZ) test for animal models of testing epileptic medications in acute seizures. (3)

A
  • Subcutaneous injection of a convulsive dose of PTZ
  • Rodents may develop clonic seizures over next 30 mins
  • Test for anti-seizure activity against nonconvulsive seizures
84
Q

Describe a ‘success story’ of the subcutaneous pentylenetetrazole (PTZ) seizure test for animal models of testing epileptic medications in acute seizures. (1)

A

Ethosuximide is shown in this model to be effective in nonconvulsive seizures, and in practice it is effective in childhood absence seizures.

85
Q

The maximal electroshock seizure (MES) test and the subcutaneous pentylenetetrazole (PTZ) seizure test are animal models used to screen for anti-epileptic drugs.

Give two drawbacks of using these tests in drug discovery. (2)

A
  • Unable to predict drug responses to all seizure types
  • These models only simulate acute seizures - the kindling model may be more effective for long-term seizure activity
86
Q

Give two very general targets for anti-epileptic drugs. (2)

A
  • Ion channels
  • Neurotransmitter receptors
87
Q

Complete the sentence relating to anti-epileptic drugs. (1)

Antiepileptic drugs work by targeting key regulators of ……………………….

A

neuronal excitability

88
Q

Name a specific ion channel which is a key target for anti-epileptic drugs. (1)

A

Sodium channels

89
Q

What are the three states that voltage-gated sodium channels can exist in? (3)

A
  • Resting state
  • Activated state
  • Inactivated state
90
Q

Give three general roles of sodium channels in neurones. (3)

A
  • Action potentials
  • Transmitter release
  • Subthreshold neuronal properties in dendrites
91
Q

Describe how the action of antiepileptic drugs at sodium channels is related to the state that the channel is in. (3)

A
  • Drugs bind poorly to resting sodium channel
  • Block increases with repetitive action/depolarisations (however onset is generally slow)
  • Therefore antiepileptic drugs are use and voltage dependent
92
Q

Give two way by which antiepileptic drugs may alter sodium channels in the treatment of acute seizures. (2)

A
  • Prolong inactivated state of channel
  • Reduce burst firing (however some bursting is able to occur due to slow onset)
93
Q

True or false? Explain your answer if appropriate. (1)

The main action of antiepileptic drugs on sodium channels may be to stop the spread of the seizure, rather than to cause all seizure activity to cease.

A

True

94
Q

Some epilepsies are caused by mutations in sodium channels with increased INa.P

What is meant by increased INa.P? (1)

Is this a gain or loss of function mutation? (1)

Why is the phenotype of these mutations difficult to predict? (1)

A

Persistent sodium current

Gain of function

There is a wide distribution of different Na channel subtypes across the neurone, and across inhibitory and excitatory networks.

95
Q

Patients with severe loss of function mutations in sodium channels on inhibitory neurones might have epilepsy worsened by what commonly-used anti-epileptic drug? (1)

Give an example of an epilepsy type caused by loss of function mutations in sodium channels on inhibitory neurones. (1)

A

Lamotrigine

Severe myoclonic epilepsy of infancy

96
Q

Apart from sodium channels, give five other more specific targets for anti-epileptic drugs. (5)

A
  • GABAergic neurotransmission
  • Glutamatergic neurotransmission
  • Potassium channels
  • Calcium channels
  • Carbonic anhydrase
97
Q

Give three examples of anti-epileptic drugs that work by altering GABAergic neurotransmission. (3)

A
  • Benzodiazepines
  • Barbiturates
  • Vigabatrin
98
Q

Give an example of an anti-epileptic drug which works by antagonising AMPA receptors, therefore reducing glutamatergic neurotransmission. (1)

A

Perampanel

99
Q

Give an example of a (now discontinued) anti-epileptic drug which works by affecting potassium channels. (1)

A

Retigabine

100
Q

Give an example of an anti-epileptic drug which works by affecting calcium channels. (1)

A

Pregabalin

101
Q

Acetazolamide can be affective in treating epilepsy by targeting carbonic anhydrase.

Describe what type of drug acetazolamide is, and the mechanism by which it works in epilepsy. (2)

A

It is a diuretic

which alters neuronal pH (makes it more acidic) by blocking carbonic anhydrase

102
Q

Give three possible non-pharmacological treatments for epilepsy. (3)

A
  • Resection of epileptic focus
  • Vagal nerve stimulation (potentially also deep brain stimulation)
  • Ketogenic diet
103
Q

What is status epilepticus? (1)

A

Epileptic seizures which are not stopping, or recurrent seizures without recovery of consciousness.

104
Q

Suggest a reason why HPA negative feedback may be impaired in depression. (1)

A

Malfunction of glucocorticoid receptors

105
Q

Suggest two reasons why adult neurogenesis may be disrupted in MDD. (2)

A
  • Lack of BDNF
  • Malfunction of glucocorticoid receptors
106
Q

True or false? Explain your answer if appropriate. (1)

In MDD, the volume of the amygdala is increased.

A

False - it is reduced

107
Q

Give the main role of ACh in the PNS. (1)

A

Muscle contraction

108
Q

Give the main roles of ACh in the CNS. (2)

A
  • Motor control
  • Cognition (attention, learning, memory)
109
Q

Very briefly describe an experiment which led to the discovery of ACh controlling the heart. (3)

A
  • Heart electrically stimulated
  • Fluid around heart collected
  • When fluid was transferred to another heart (which was not innervated), it could control the other heart, so chemical (ACh) must be controlling heart
110
Q

Cholinergic projection neurones in the brain arise from 8 clusters, found in three distinct brain areas.

Name the three brain areas from which cholinergic neurones arise. (3)

A
  • Medial septal group (basal forebrain)
  • Pontine cholinergic system / caudal midbrain
  • Midbrain
111
Q

Cholinergic neuronal clusters 1-4 arise from the basal forebrain and are referred to as the medial septal group.

Give two brain regions which are targeted by these neurones. (2)

Give three roles of these neurones. (3)

A
  • Cortex
  • Limbic system

ROLES:

  • Attention
  • Learning
  • Memory
112
Q

Cholinergic neuronal clusters 5-6 arise from the caudal midbrain and are referred to as the pontine cholinergic system.

Give three brain regions which are targeted by these neurones. (3)

Give three roles of these neurones. (3)

A

Thalamus

Midbrain

Cerebellum

ROLES:

  • Sleep
  • Arousal
  • Motor function
113
Q

Cholinergic neuronal clusters 7-8 arise from the midbrain.

Give a brain region which is targeted by these neurones. (1)

Give two roles of these neurones. (2)

A

Target the brainstem (particularly the midbrain)

ROLES:

  • Sensory function
  • Motor function
114
Q

Which group of cholinergic neurones are lost in Alzheimer’s disease? (1)

A

Nucleus of Meynert, in the basal forebrain (or medial septal group)

115
Q

What is the role of ACh in the somatic nervous system, and what receptor/s are involved? (2)

A

Contraction of skeletal muscle

via nAChRs at NMJ

116
Q

What is the role of ACh in the sympathetic nervous system? (3)

Whet receptors at what locations are responsible for these functions? (3)

A

Release of adrenaline/noradrenaline from adrenal medulla

nAChR in adrenal medulla

Release of noradrenaline from postsynaptic neurones

nAChR at sympathetic ganglion

Direct control of sweat glands

via nAChR in ganglia and mAChR located in effector organs

117
Q

Give three roles of ACh in the parasympathetic nervous system. (3)

Via which receptors (and their locations) are these roles carried out? (2)

A
  • Control of heart rate
  • Salivation
  • Digestion

Via nAChRs in ganglia

and mAChRs at effector organs

118
Q

Describe the two sets of autonomic PNS neurones, in terms of where their cell bodies are and where they terminate/synapse. (4)

A

PREGANGLIONIC:

  • Cell bodies in brain or spinal cord
  • Synapse in ganglia near/in effector organs

POSTGANGLIONIC:

  • Cell bodies in ganglia
  • Synapse on effector organ
119
Q

Briefly describe the synthesis of acetylcholine, in terms of the molecular changes which occur. (2)

A

Acetyl group from acetyl-CoA

added to choline

120
Q

Name the enzyme which catalyses the addition of an acetyl group to choline to form ACh. (1)

A

Choline acetyltransferase (ChAT)

121
Q

Acetyl-CoA is an essential molecule needed to form the neurotransmitter ACh.

What is the body’s source of Acetyl-CoA? (1)

A

Glucose breakdown

122
Q

Choline is an essential molecule needed to form the neurotransmitter ACh.

What is the body’s source of choline? (1)

Give some examples. (6)

A

Diet

  • Egg yolks
  • Liver
  • Fish
  • Grains
  • Nuts
  • Soya
123
Q

Name the transporter which loads acetylcholine into synaptic vesicles. (1)

A

Vesicular acetylcholine transporter (VAChT)

124
Q

How many ACh molecules are usually loaded into each 40-50nm synaptic vesicle? (1)

A

10,000

125
Q

The metabolism of ACh results in what two products being formed? (2)

A
  • Choline
  • Acetate
126
Q

Name the enzyme which catalyses the metabolism of acetylcholine. (1)

A

Acetylcholinesterase (AChE)

127
Q

Where is AChE located, so where does the breakdown of ACh occur? (1)

A

In the synapse

128
Q

Of the products of ACh breakdown, which is taken back up into the presynaptic cell? (1)

What happens to it once it has been taken back up? (1)

A

Choline

Used for resynthesis

129
Q

What is the rate-limiting step in ACh synthesis? (1)

A

Choline reuptake

130
Q

Describe the transporter which takes choline (from the breakdown of ACh) back up into the presynaptic terminal. (2)

A

Choline-Na+ co-transporter

which is energy dependent

131
Q

What is the main method by which ACh neurotransmission is terminated in the synapse and at the NMJ? (1)

A

Breakdown by AChE

132
Q

Why isn’t cholinergic neurotransmission terminated by the reuptake transporter at the synapse/NMJ? (1)

A

Reuptake transporter only transports choline so ACh must be broken down before choline is taken back up.

133
Q

Why is it important for cholinergic neurotransmission to be terminated quickly at the synapse/NMJ? (1)

A

To maintain fine motor control

134
Q

True or false? Explain your answer if appropriate. (1)

ACh causes muscle contraction of skeletal, cardiac, and smooth muscle.

A

False - ACh causes voluntary contraction of skeletal muscle, and does affect cardiac and smooth muscle but may be more relaxing

135
Q

What is a motor unit? (1)

A

A motor unit consists of a somatic motor neurone plus all the muscle fibres it innervates.

136
Q

Approximately how many neurones (how many synapses) innervate a single muscle fibre? (1)

A

One

137
Q

Describe where the cell bodies of alpha motor neurones are located, and where the neurones terminate. (2)

Which neurotransmitter do they use? (1)

A

Cell bodies in ventral horn of spinal cord

Terminate at NMJ of skeletal muscle

Use ACh

138
Q

As well as quick deactivation of cholinergic neurotransmission, give another technique which allows fine motor control of muscles. (1)

A

Each muscle fibre only belongs to one motor unit.

139
Q

Briefly describe the steps involved in an alpha motor neurone causing a muscle contraction at the NMJ. (5)

A
  • Action potential releases ACh from nerve terminal
  • ACh activates nicotinic receptors on muscle fibres
  • ACh broken down by acetylcholinesterase
  • Depolarisation of muscle membrane, which propagates and activates voltage-gated sodium channels
  • Muscle contraction
140
Q

Describe the mechanism by which an action potential in an alpha motor neurone always causes a muscle contraction. (1)

A

Each action potential results in 8-10x ACh being released than what is required

141
Q

How do nerve gases have their effects on the body? (2)

A

They are potent AChE inhibitors

So prevent degradation of ACh

And unopposed muscle contraction, paralysis, and asphyxiation

142
Q

Name the two general types of ACh receptors. (1)

A
  • Nicotinic
  • Muscarinic
143
Q

Are nicotinic AChRs inotropic or metabotropic? (1)

A

Inotropic

144
Q

Are nicotinic ACh receptors excitatory or inhibitory? (1)

A

Excitatory

145
Q

How many subunits make up each nicotinic ACh receptor? (1)

A

5 (pentameric)

146
Q

How many subtypes of nicotinic ACh receptors are there? (1)

A

11

147
Q

Nicotinic ACh receptors are mainly permeable to which ions? (1)

A

Na

K

148
Q

Are nicotinic ACh receptors found in the PNS or CNS? (1)

A

Both

149
Q

True or false? Explain your answer if appropriate. (1)

Homomeric nAChRs are either made up of all alpha or all beta subunits.

A

False - they are made up of all alpha subunits, because each receptor must contain at least 2 alpha subunits

150
Q

How many alpha and how many beta subunits must each nAChR contain? (2)

A

2 alpha units

Doesn’t matter how many beta units

151
Q

Give five properties of nAChRs which are mediated by subunit composition. (5)

A
  • Ion selectivity
  • Agonist affinity
  • Localisation
  • Kinetics
  • Desensitisation
152
Q

Describe what is meant by N1/Nm and N2/Nn nicotinic acetylcholine receptors. (2)

A

N1/Nm are muscle-type receptors found at teh NMJ

N2/Nn are neuronal receptors found on neurones

153
Q

Name the subunits found on NMJ nicotinic AChRs. (5)

A

a1, a1, b1, y, delta in embryonic form

a1, a1, b1, e, delta in adult form

154
Q

The N1/Nm nicotinic ACh receptor changes its subunits between embryonic and adult form.

Describe two functional differences between the embryonic and adult forms of this receptor. (2)

A

ADULT FORM HAS:

  • higher conductance
  • shorter opening time
155
Q

True or false? Explain your answer if appropriate. (1)

All N2/Nn nicotinic ACh receptors are made up of combinations of alpha, beta, epsilon, gamma, and delta subunits.

A

False - they are made up of alpha and beta subunits.

epsilon, gamma, and delta subunits are only found on N1/Nm receptors.

156
Q

What is meant by homomeric and heteromeric nicotinic ACh receptors? (2)

A

Homomeric feature only alpha subunits

Heteromeric feature both alpha and beta subunits

157
Q

Name the specific alpha and beta subunits which can form parts of nicotinic ACh receptors. (2)

A

a2-a10

b2-b4

158
Q

Each nicotinic ACh receptor binds how many ACh molecules? (1)

A

One

159
Q

Are muscarinic ACh receptors inotropic or metabotropic? (1)

A

Metabotropic (GPCRs)

160
Q

How many subtypes of muscarinic ACh receptors are there? (1)

Name these subtypes.

A

5

M1-M5

161
Q

Are muscarinic ACh receptors excitatory or inhibitory? (1)

Explain your answer. (2)

A

Both

M1, M3, M5 are excitatory

M2, M4 are inhibitory

162
Q

M1, M3, and M5 ACh receptors are coupled to which G protein? (1)

A

Gq

163
Q

M2 and M4 ACh receptors are coupled to which G protein? (1)

A

Gi

164
Q

Which subtypes of muscarinic ACh receptors are found in the CNS?

A

All 5 subtypes (M1-M5)

165
Q

Which subtypes of muscarinic ACh receptors are found in the PNS and other tissues?

A

M1-M4

166
Q

Where are M1 ACh receptors typically found in high concentrations? (2)

A

On neurones

In enteric nervous system

167
Q

Where are M3 ACh receptors typically found in high concentrations? (2)

A

Glandular

Vascular

168
Q

Where are M5 ACh receptors typically found in high concentrations? (1)

A

CNS

169
Q

Where are M2 ACh receptors typically found in high concentrations? (1)

A

Cardiac muscle

170
Q

Where are M4 ACh receptors typically found in high concentrations? (1)

A

CNS

171
Q

M1, M3, and M5 ACh receptors have excitatory functions.

Give six functions of these receptors. (6)

A
  • CNS excitation
  • Gastric acid secretion
  • Gastrointestinal motility
  • Glandular secretion
  • Contraction of visceral smooth muscle
  • Vasodilation (via NO)
172
Q

M2 and M4 ACh receptors have inhibitory functions.

Give three functions of these receptors. (3)

A
  • Cardiac inhibition
  • Presynaptic inhibition
  • Neuronal inhibition
173
Q

Which muscarinic ACh receptors are thought to mediate PNS effects on the heart? (1)

A

M2

174
Q

Which specific type of ACh receptor is found in the adrenal medulla to facilitate release of adrenaline via the sympathetic nervous system? (1)

A

N2/Nn

175
Q

Give two subtypes of muscarinic ACh receptors which are thought to control exocrine gland secretion. (2)

A

M2
M3

176
Q

Give two subtypes of muscarinic ACh receptors which are thought to control pupillary constriction/relaxation. (2)

A

M2
M3

177
Q

Describe the neuromodulatory effects of both nicotinic and muscarinic ACh receptors in the cortex and hippocampus. (2)

A

Nicotinic receptors increase NT release

Muscarinic receptors both increase and decrease NT release

178
Q

Give two areas of the CNS which have large distributions of ACh receptors. (2)

A

Cortex

Hippocampus

179
Q

Complete the passage relating to cholinergic neurotransmission. (4)

Manipulating ACh levels in the brain affects a range of cognitive functions, particularly ……………………, …………………………, and ………………………..
ACh …………………….. is an important factor which contributes to normal age-related cognitive decline.

A

Attention

Learning

Memory

Depletion

180
Q

Very briefly describe a general piece of evidence supporting the fact that ACh plays a role in cognition. (1)

A

Drugs that manipulate cholinergic neurotransmission can affect cognition

181
Q

What would be the expected effect of nicotine and muscarine on cognition? (1)

Explain your answer. (1)

A

Improvement in cognitive function

Because they are AChR agonists and may improve cognition when acting on excitatory receptors

182
Q

What would be the predicted effect of AChE inhibitors on cognition in Alzheimer’s disease? (1)

Explain your answer. (1)

A

Improvement in cognitive function

They prevent ACh degradation and increase ACh levels in the synapse

183
Q

How are irreversible AChE inhibitors thought to affect cognition? (1)

A

Probably no effect because they are toxic and would kill you

184
Q

What effect would you predict AChR antagonists to have on cognition? (1)

Explain your answer. (1)

A

Produce cognitive/memory deficits similar to AD

Because they block the effects of ACh at receptors

185
Q

Give two examples of AChR antagonists which could be used to produce animal models of Alzheimer’s disease and cognitive decline. (2)

A

Scopolamine

Atropine

186
Q

AChR antagonists can be used to produce memory/cognitive impairments in animals to produce models of AD/cognitive decline.

Why might these types of drugs be prescribed in humans? (1)

A

For peripheral cholinergic issues

eg. urinary incontinence

187
Q

Complete the passage about testing the roles of cholinergic neurotransmission. (2)

Vigilance tasks can be used to test the role of ACh. These kinds of tasks require ……………………, which is thought to be dependent on ……………………

A

sustained attention

excitatory ACh neurotransmission

188
Q

Briefly describe a vigilance task which could be used to investigate the role of ACh in cognition. (3)

A
  • Letters, digits, or shapes presented in random order
  • Subjects must respond to specified targets (eg. when two subsequent shapes are the same)
  • Measure response time and omissions/false alarms
189
Q

Describe the expected effect of scopolamine on vigilance task performance. (1)

A

Impaired performance

(slower responses and more errors)

190
Q

Describe the expected effect of nicotine on vigilance task performance. (1)

A

Improved task performance

(faster responses and less errors)

191
Q

Describe how the Y maze could be used to screen for the effects of Alzheimer’s drugs. (3)

A
  • Y maze assesses cognition and memory
  • Use scopolamine model of cognitive impairment
  • Test drugs for reversal of scopolamine-induced cognitive deficits
192
Q

Describe how cholinergic neurotransmission may be associated with schizophrenia. (2)

A

Mutations in nicotinic a7 receptor increases chance of developing schizophrenia

Smoking unusually prevalent in schizophrenia, is this to reverse cognitive deficits?

193
Q

Describe how cholinergic neurotransmission may be associated with Parkinson’s Disease. (1)

A

Dopaminergic activity is heavily regulated by both muscarinic and nicotinic receptor activity

194
Q

Describe how cholinergic neurotransmission may be associated with epilepsy. (1)

A

Mutations in nicotinic receptors associated with autosomal dominant nocturnal frontal lobe epilepsy

195
Q

Describe how cholinergic neurotransmission may be associated with addiction. (2)

A

Nicotine activates the mesolimbic DA pathways resulting in addiction

Deleting M5 receptors on DAergic neurones reduces reinforcement and withdrawal related behaviours (could this lead to treatments for addiction?)

196
Q

Describe how cholinergic neurotransmission may be associated with Alzheimer’s disease. (2)

A

Many neurological and psychiatric impairments seen in AD are linked to disruption of the cholinergic system

AChE inhibitors are often used to treat these symptoms

197
Q

ACh receptors are abundant throughout the brain, however different subtypes may have different effects.

This might be due to the different subtypes of AChR being formed of different proteins or being linked to different G proteins.

Suggest another reason for the differing effects. (1)

A

Differences in expression profiles between subtypes (ie. different subtypes are expressed in different brain regions)

Neuroscience Y2S2 (15 decks)

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