Neurobiology of Disease 6 Flashcards
(198 cards)
1
Q
Is epilepsy thought to be monogenetic or polygenetic, where there is a genetic cause? (1)
A
Can be either
2
Q
Define ‘epilepsy’. (2)
A
A pathologic and enduring tendency to have recurrent seizures
and the neurobiological, cognitive, psychological, and social consequences.
3
Q
Give a structural cause of epilepsy. (1)
A
Malformations of development
(ie, where brain development results in a malformation)
4
Q
Give four acquired causes of epilepsy. (4)
A
- Trauma
- Infection
- Tumour
- Stroke
5
Q
When are structural/malformation causes of epilepsy most likely to present? (1)
A
Early childhood
6
Q
When might polygenetic causes of epilepsy present? (1)
A
Later in life
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.
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
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)
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)
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
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)
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)
14
Q
Is generalised epilepsy more likely to be due to genetics or brain lesions? (1)
A
Genetics - multiple mutations each conferring small risk
15
Q
Name three specific types of generalised seizures. (1)
A
Typical absence seizure
Myoclonic
Tonic-clonic
16
Q
When do absence seizures usually begin? (1)
A
Childhood
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
18
Q
Describe the aura and post-ictal state in absence seizures. (2)
A
No aura
No post-ictal state
19
Q
Describe a myoclonic seizure. (2)
A
Sudden, brief, shock-like muscle contractions
Which are usually bilateral in the arms
20
Q
Give three things that can precipitate/bring on myoclonic seizures. (3)
A
- Mornings (seizures worse in mornings)
- Sleep deprivation
- Alcohol
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
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
23
Q
Describe the typical EEG pattern seen in an absence seizure. (2)
A
3Hz
spike and wave pattern
24
Q
Why are absence seizures described as an ‘electroclinical syndrome’? (1)
A
Features both clinical symptoms and a typical EEG pattern
25
Are atonic seizures usually generalised or focal seizures? (1)
Usually generalised
26
Describe an atonic seizure. (2)
Sudden loss of muscle tone
Children often fall to the floor
27
Describe the duration and recovery of an atonic seizure. (2)
- Brief duration
- Quick recovery
28
Why are atonic seizures so dangerous? (2)
They often occur in children
and falling to the floor can cause serious injuries (including to the head)
29
What is it called when a seizure starts in one hemisphere and propagates to include the opposite hemisphere? (1)
Secondary generalised seizure
30
How do the symptoms of a secondary generalised seizure change throughout the duration of the seizure? (1)
The symptoms evolve to reflect the brain regions involved as the seizure propagates.
31
What is the difference between a partial seizure and a focal seizure? (1)
Partial is old terminology and focal is new terminology
32
What is the most common type of focal epilepsy? (1)
Temporal lobe epilepsy
33
Give three symptoms experienced during the warning (aura) phase of a temporal lobe seizure. (3)
- Epigastric rising sensation
- Olfactory and gustatory cues
- Deja vu
34
True or false? Explain your answer if appropriate. (1)
Temporal lobe seizures usually do not feature a post-ictal phase.
False - they do
34
Give five symptoms/features commonly seen in a temporal lobe seizure. (5)
- Loss of awareness
- Arrest reaction
- Blank stare
- Oral automatisms (lip-smacking)
- Manual automatisms
35
True or false? Explain your answer if appropriate. (1)
Seizures are a phenomenon unique to mammals.
False - it has been suggested that even invertebrate organisms such as C.elegans, Drosophila, and zebrafish are able to show epileptic activity.
36
Give an advantage of using non-human, and potentially invertebrate models to investigate seizures. (1)
Wider range of studies can be carried out with less ethical considerations.
37
Give three techniques/experimental set-ups that are often used in experiments investigating seizures. (3)
- Hippocampal slices exposed to acute seizure-provoking stimuli
- Animals with induced CNS injury causing seizures
- Rodent genetic models
38
Give three general types of stimuli that can be used to induce seizures in hippocampal slices. (3)
- Electrical stimulation
- Bath medium
- Drugs
39
Give two alterations to the bath medium that can be used to induce seizures in hippocampal slices. (2)
- Low magnesium
- Low calcium
40
Give 2 drugs (and what classes they are) which can be used to induce seizures in hippocampal slices. (2)
4-aminopyridine (potassium channel blocker)
Bicuculline (GABA blocker)
41
What is meant by measuring 'local field potentials (LFP)' when studying seizures? (1)
Using micro EEGs to record summed synaptic activity from thousands of neurones
42
What is meant by measuring 'spikes' when studying seizures? (1)
A measure of a single neurone firing (otherwise known as an action potential)
43
What is an inter-ictal spike, when referring to seizures and seizure activity in the brain? (1)
200ms event which occurs in between seizures, and is indicative of an area prone to seizures
44
Give the four stages of focal seizure activity on a neuronal/electrophysiological level. (4)
- Initiation
- Synchronisation
- Propagation
- Termination
45
Give three advantages of using hippocampal slice experiments to investigate seizure activity. (3)
- Realistic epileptic discharges can be created
- Can obtain very detailed neurophysiology and neuropharmacology measurements
- More humane than using animals
46
Give three disadvantages of using hippocampal slice experiments to investigate seizure activity. (3)
- 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
47
Give four aspects of the experimental set-up/design of hippocampal slice studies that may affect the results seen. (4)
- 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?
48
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
Neuronal bursting
glutamate
GABA
Glial cells
extracellular
gap
49
True or false? Explain your answer if appropriate. (1)
For a focal seizure to occur, both 'epileptic neurones' and 'epileptic networks' are needed.
True
50
Give three features of an epileptic network in the brain needed for synchrony. (3)
- Divergent connections (one neurone connecting with many others)
- Effective synapses
- Minimum aggregate of neurones in a highly-connected network
51
Give four molecular/cellular events which occur during the initiation phase of a focal seizure. (4)
- High frequency oscillations
- Bursting of excitatory neurones
- Overcoming of inhibition
- Micro-seizures coalescing to trigger the main event
52
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 ..............................
Local
long-range
Synaptic
Non-synaptic
53
Give three non-synaptic events which may occur in order to produce synchronisation of neurones and neuronal networks during a focal seizure. (3)
- Gap junctions
- Field events
- Micro-environment changes (eg. K concentration)
54
Give six molecular/cellular events which may occur during or lead to termination of a focal seizure. (6)
- Synaptic inhibition
- Depolarisation block
- Depletion of synaptic components (eg. vesicles, ATP, and NTs)
- Intracellular acidification
- Hyperpolarisation due to K channels
- Effects of neuromodulators
55
Give three examples of neuromodulators which may play a role in termination of focal seizures. (3)
- Adenosine
- Opioids
- Endocannabinoids
56
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.
Cortex
Thalamus
Corticothalamic
57
Briefly describe how a generalised seizure may propagate and cause loss of consciousness. (3)
Name the various networks and brain areas involved.
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
58
Name a drug which might be particularly effective in generalised seizures and describe why it might be effective. (2)
Ethosuximide
Because it acts on the thalamus, which is implicated in generalised seizures.
59
Describe what is meant by epileptogenesis. (1)
The process by which a brain network that was previously normal is functionally altered toward increased seizure susceptibility.
60
Give five factors (either physiological or in experimental conditions) which can lead to epileptogenesis. (5)
- Head trauma
- Stroke
- Drugs
- Electrical activity (inducing a prolonged seizure)
- Cortical iron implantation
61
Describe the status epilepticus animal model of epileptogenesis. (1)
Induce a very long seizure but rescue animal before death
62
How can febrile seizures in children lead to epilepsy? (2)
If seizure is long
can lead to temporal lobe scarring and focal epilepsy
63
Give two drugs that can be used to induce status epilepticus in animal models. (2)
Pilocarpine
Kainate
64
In addition to using drugs, give another method of inducing status epilepticus in animal models. (1)
Electrical stimulation
65
Give three types of animal models used to investigate epileptogenesis. (3)
- Status epilepticus
- Injury (head trauma / stroke / cortical iron implantation)
- Kindling
66
Briefly describe the kindling method of modelling epileptogenesis in animals. (1)
Electrode inserted into hippocampus or amygdala, and repeat sub-convulsive stimuli applied
67
For which experimental use is a kindling animal model of epileptogenesis particularly useful? (1)
Testing drugs for focal onset seizures
68
Describe how the brain changes throughout the early stages of kindling to the late stages (overkindling) when producing an animal model of epileptogenesis. (2)
Early stages increases inhibition
Over-kindling (100+ stimuli) causes cell loss (potentially of inhibitory interneurones), abnormal neuronal sprouting, and spontaneous seizures.
69
As well as spontaneous seizures, give two cognitive deficits that may be experienced in rodents due to the kindling method of modelling epileptogenesis. (2)
Memory deficits
Spatial deficits
70
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.
False - it is permanent, and can occur in various species, including primates
71
Give four changes that are seen in a rodent model of epileptogenesis, once the rodent is in the 'fully kindled state'. (4)
- Enhanced seizure susceptibility
- Behavioural and cognitive alterations
- Physiological and neurochemical alterations
- Discrete histological alterations (eg. neurodegeneration and sprouting)
72
Give six structural/gross changes that are thought to occur in epileptogenesis. (6)
- Cell loss (inhibitory interneurones, leading to disinhibited circuits)
- Axonal sprouting (leading to extra excitatory circuits)
- Neurogenesis
- Gliosis
- Neuroinflammation
- BBB breakdown
73
Give four molecular changes that are thought to occur in epileptogenesis. (4)
- Changes to ion channels
- Changes to receptors
- Changes to neurotransmitter transporters
- Changes to neuromodulators (such as peptides and endocannabinoids)
74
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)
Na
K
Ca
Cl
HCO3
Acquired channelopathies
75
Name four receptors which might be altered during epileptogenesis. (4)
GABA
AMPA
NMDA
ACh
76
Give two functional changes that are thought to occur in epileptogenesis. (2)
- Gap junctions
- Glial cells (eg. buffering of extracellular environment)
77
Give four general considerations to be taken into account when treating epilepsy. (4)
- Is the diagnosis correct?
- Matching of drug treatment to syndrome and lifestyle
- General lifestyle advice
- Identifying who might be a surgical candidate
78
Give four lifestyle aspects that patients may need to be advised about in epilepsy. (4)
- Alcohol
- Drugs
- Late nights
- Driving
79
Give a lifestyle consideration to be taken into account when prescribing drugs for epilepsy. (1)
Valproate cannot be used in pregnancy
80
Give two animal models of acute seizures which can be used to screen for anti-epileptic drugs. (2)
Maximal electroshock seizure (MES) test
Subcutaneous pentylenetetrazole (PTZ) seizure test
81
Describe the maximal electroshock seizure (MES) test for animal models of testing epileptic medications in acute seizures. (3)
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
Give an advantage and disadvantage of the maximal electroshock seizure (MES) test for animal models of testing epileptic medications in acute seizures. (2)
ADVANTAGE:
- Led to the discovery of phenytoin
DISADVANTAGE:
- Levetiracetam not effective in this model but is effective in clinical situations
83
Describe the subcutaneous pentylenetetrazole (PTZ) test for animal models of testing epileptic medications in acute seizures. (3)
- 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
Describe a 'success story' of the subcutaneous pentylenetetrazole (PTZ) seizure test for animal models of testing epileptic medications in acute seizures. (1)
Ethosuximide is shown in this model to be effective in nonconvulsive seizures, and in practice it is effective in childhood absence seizures.
85
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)
- 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
Give two very general targets for anti-epileptic drugs. (2)
- Ion channels
- Neurotransmitter receptors
87
Complete the sentence relating to anti-epileptic drugs. (1)
Antiepileptic drugs work by targeting key regulators of ............................
neuronal excitability
88
Name a specific ion channel which is a key target for anti-epileptic drugs. (1)
Sodium channels
89
What are the three states that voltage-gated sodium channels can exist in? (3)
- Resting state
- Activated state
- Inactivated state
90
Give three general roles of sodium channels in neurones. (3)
- Action potentials
- Transmitter release
- Subthreshold neuronal properties in dendrites
91
Describe how the action of antiepileptic drugs at sodium channels is related to the state that the channel is in. (3)
- 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
Give two way by which antiepileptic drugs may alter sodium channels in the treatment of acute seizures. (2)
- Prolong inactivated state of channel
- Reduce burst firing (however some bursting is able to occur due to slow onset)
93
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.
True
94
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)
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
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)
Lamotrigine
Severe myoclonic epilepsy of infancy
96
Apart from sodium channels, give five other more specific targets for anti-epileptic drugs. (5)
- GABAergic neurotransmission
- Glutamatergic neurotransmission
- Potassium channels
- Calcium channels
- Carbonic anhydrase
97
Give three examples of anti-epileptic drugs that work by altering GABAergic neurotransmission. (3)
- Benzodiazepines
- Barbiturates
- Vigabatrin
98
Give an example of an anti-epileptic drug which works by antagonising AMPA receptors, therefore reducing glutamatergic neurotransmission. (1)
Perampanel
99
Give an example of a (now discontinued) anti-epileptic drug which works by affecting potassium channels. (1)
Retigabine
100
Give an example of an anti-epileptic drug which works by affecting calcium channels. (1)
Pregabalin
101
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)
It is a diuretic
which alters neuronal pH (makes it more acidic) by blocking carbonic anhydrase
102
Give three possible non-pharmacological treatments for epilepsy. (3)
- Resection of epileptic focus
- Vagal nerve stimulation (potentially also deep brain stimulation)
- Ketogenic diet
103
What is status epilepticus? (1)
Epileptic seizures which are not stopping, or recurrent seizures without recovery of consciousness.
104
Suggest a reason why HPA negative feedback may be impaired in depression. (1)
Malfunction of glucocorticoid receptors
105
Suggest two reasons why adult neurogenesis may be disrupted in MDD. (2)
- Lack of BDNF
- Malfunction of glucocorticoid receptors
106
True or false? Explain your answer if appropriate. (1)
In MDD, the volume of the amygdala is increased.
False - it is reduced
107
Give the main role of ACh in the PNS. (1)
Muscle contraction
108
Give the main roles of ACh in the CNS. (2)
- Motor control
- Cognition (attention, learning, memory)
109
Very briefly describe an experiment which led to the discovery of ACh controlling the heart. (3)
- 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
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)
- Medial septal group (basal forebrain)
- Pontine cholinergic system / caudal midbrain
- Midbrain
111
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)
- Cortex
- Limbic system
ROLES:
- Attention
- Learning
- Memory
112
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)
Thalamus
Midbrain
Cerebellum
ROLES:
- Sleep
- Arousal
- Motor function
113
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)
Target the brainstem (particularly the midbrain)
ROLES:
- Sensory function
- Motor function
114
Which group of cholinergic neurones are lost in Alzheimer's disease? (1)
Nucleus of Meynert, in the basal forebrain (or medial septal group)
115
What is the role of ACh in the somatic nervous system, and what receptor/s are involved? (2)
Contraction of skeletal muscle
via nAChRs at NMJ
116
What is the role of ACh in the sympathetic nervous system? (3)
Whet receptors at what locations are responsible for these functions? (3)
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
Give three roles of ACh in the parasympathetic nervous system. (3)
Via which receptors (and their locations) are these roles carried out? (2)
- Control of heart rate
- Salivation
- Digestion
Via nAChRs in ganglia
and mAChRs at effector organs
118
Describe the two sets of autonomic PNS neurones, in terms of where their cell bodies are and where they terminate/synapse. (4)
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
Briefly describe the synthesis of acetylcholine, in terms of the molecular changes which occur. (2)
Acetyl group from acetyl-CoA
added to choline
120
Name the enzyme which catalyses the addition of an acetyl group to choline to form ACh. (1)
Choline acetyltransferase (ChAT)
121
Acetyl-CoA is an essential molecule needed to form the neurotransmitter ACh.
What is the body's source of Acetyl-CoA? (1)
Glucose breakdown
122
Choline is an essential molecule needed to form the neurotransmitter ACh.
What is the body's source of choline? (1)
Give some examples. (6)
Diet
- Egg yolks
- Liver
- Fish
- Grains
- Nuts
- Soya
123
Name the transporter which loads acetylcholine into synaptic vesicles. (1)
Vesicular acetylcholine transporter (VAChT)
124
How many ACh molecules are usually loaded into each 40-50nm synaptic vesicle? (1)
10,000
125
The metabolism of ACh results in what two products being formed? (2)
- Choline
- Acetate
126
Name the enzyme which catalyses the metabolism of acetylcholine. (1)
Acetylcholinesterase (AChE)
127
Where is AChE located, so where does the breakdown of ACh occur? (1)
In the synapse
128
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)
Choline
Used for resynthesis
129
What is the rate-limiting step in ACh synthesis? (1)
Choline reuptake
130
Describe the transporter which takes choline (from the breakdown of ACh) back up into the presynaptic terminal. (2)
Choline-Na+ co-transporter
which is energy dependent
131
What is the main method by which ACh neurotransmission is terminated in the synapse and at the NMJ? (1)
Breakdown by AChE
132
Why isn't cholinergic neurotransmission terminated by the reuptake transporter at the synapse/NMJ? (1)
Reuptake transporter only transports choline so ACh must be broken down before choline is taken back up.
133
Why is it important for cholinergic neurotransmission to be terminated quickly at the synapse/NMJ? (1)
To maintain fine motor control
134
True or false? Explain your answer if appropriate. (1)
ACh causes muscle contraction of skeletal, cardiac, and smooth muscle.
False - ACh causes voluntary contraction of skeletal muscle, and does affect cardiac and smooth muscle but may be more relaxing
135
What is a motor unit? (1)
A motor unit consists of a somatic motor neurone plus all the muscle fibres it innervates.
136
Approximately how many neurones (how many synapses) innervate a single muscle fibre? (1)
One
137
Describe where the cell bodies of alpha motor neurones are located, and where the neurones terminate. (2)
Which neurotransmitter do they use? (1)
Cell bodies in ventral horn of spinal cord
Terminate at NMJ of skeletal muscle
Use ACh
138
As well as quick deactivation of cholinergic neurotransmission, give another technique which allows fine motor control of muscles. (1)
Each muscle fibre only belongs to one motor unit.
139
Briefly describe the steps involved in an alpha motor neurone causing a muscle contraction at the NMJ. (5)
- 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
Describe the mechanism by which an action potential in an alpha motor neurone always causes a muscle contraction. (1)
Each action potential results in 8-10x ACh being released than what is required
141
How do nerve gases have their effects on the body? (2)
They are potent AChE inhibitors
So prevent degradation of ACh
And unopposed muscle contraction, paralysis, and asphyxiation
142
Name the two general types of ACh receptors. (1)
- Nicotinic
- Muscarinic
143
Are nicotinic AChRs inotropic or metabotropic? (1)
Inotropic
144
Are nicotinic ACh receptors excitatory or inhibitory? (1)
Excitatory
145
How many subunits make up each nicotinic ACh receptor? (1)
5 (pentameric)
146
How many subtypes of nicotinic ACh receptors are there? (1)
11
147
Nicotinic ACh receptors are mainly permeable to which ions? (1)
Na
K
148
Are nicotinic ACh receptors found in the PNS or CNS? (1)
Both
149
True or false? Explain your answer if appropriate. (1)
Homomeric nAChRs are either made up of all alpha or all beta subunits.
False - they are made up of all alpha subunits, because each receptor must contain at least 2 alpha subunits
150
How many alpha and how many beta subunits must each nAChR contain? (2)
2 alpha units
Doesn't matter how many beta units
151
Give five properties of nAChRs which are mediated by subunit composition. (5)
- Ion selectivity
- Agonist affinity
- Localisation
- Kinetics
- Desensitisation
152
Describe what is meant by N1/Nm and N2/Nn nicotinic acetylcholine receptors. (2)
N1/Nm are muscle-type receptors found at teh NMJ
N2/Nn are neuronal receptors found on neurones
153
Name the subunits found on NMJ nicotinic AChRs. (5)
a1, a1, b1, y, delta in embryonic form
a1, a1, b1, e, delta in adult form
154
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)
ADULT FORM HAS:
- higher conductance
- shorter opening time
155
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.
False - they are made up of alpha and beta subunits.
epsilon, gamma, and delta subunits are only found on N1/Nm receptors.
156
What is meant by homomeric and heteromeric nicotinic ACh receptors? (2)
Homomeric feature only alpha subunits
Heteromeric feature both alpha and beta subunits
157
Name the specific alpha and beta subunits which can form parts of nicotinic ACh receptors. (2)
a2-a10
b2-b4
158
Each nicotinic ACh receptor binds how many ACh molecules? (1)
One
159
Are muscarinic ACh receptors inotropic or metabotropic? (1)
Metabotropic (GPCRs)
160
How many subtypes of muscarinic ACh receptors are there? (1)
Name these subtypes.
5
M1-M5
161
Are muscarinic ACh receptors excitatory or inhibitory? (1)
Explain your answer. (2)
Both
M1, M3, M5 are excitatory
M2, M4 are inhibitory
162
M1, M3, and M5 ACh receptors are coupled to which G protein? (1)
Gq
163
M2 and M4 ACh receptors are coupled to which G protein? (1)
Gi
164
Which subtypes of muscarinic ACh receptors are found in the CNS?
All 5 subtypes (M1-M5)
165
Which subtypes of muscarinic ACh receptors are found in the PNS and other tissues?
M1-M4
166
Where are M1 ACh receptors typically found in high concentrations? (2)
On neurones
In enteric nervous system
167
Where are M3 ACh receptors typically found in high concentrations? (2)
Glandular
Vascular
168
Where are M5 ACh receptors typically found in high concentrations? (1)
CNS
169
Where are M2 ACh receptors typically found in high concentrations? (1)
Cardiac muscle
170
Where are M4 ACh receptors typically found in high concentrations? (1)
CNS
171
M1, M3, and M5 ACh receptors have excitatory functions.
Give six functions of these receptors. (6)
- CNS excitation
- Gastric acid secretion
- Gastrointestinal motility
- Glandular secretion
- Contraction of visceral smooth muscle
- Vasodilation (via NO)
172
M2 and M4 ACh receptors have inhibitory functions.
Give three functions of these receptors. (3)
- Cardiac inhibition
- Presynaptic inhibition
- Neuronal inhibition
173
Which muscarinic ACh receptors are thought to mediate PNS effects on the heart? (1)
M2
174
Which specific type of ACh receptor is found in the adrenal medulla to facilitate release of adrenaline via the sympathetic nervous system? (1)
N2/Nn
175
Give two subtypes of muscarinic ACh receptors which are thought to control exocrine gland secretion. (2)
M2
M3
176
Give two subtypes of muscarinic ACh receptors which are thought to control pupillary constriction/relaxation. (2)
M2
M3
177
Describe the neuromodulatory effects of both nicotinic and muscarinic ACh receptors in the cortex and hippocampus. (2)
Nicotinic receptors increase NT release
Muscarinic receptors both increase and decrease NT release
178
Give two areas of the CNS which have large distributions of ACh receptors. (2)
Cortex
Hippocampus
179
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.
Attention
Learning
Memory
Depletion
180
Very briefly describe a general piece of evidence supporting the fact that ACh plays a role in cognition. (1)
Drugs that manipulate cholinergic neurotransmission can affect cognition
181
What would be the expected effect of nicotine and muscarine on cognition? (1)
Explain your answer. (1)
Improvement in cognitive function
Because they are AChR agonists and may improve cognition when acting on excitatory receptors
182
What would be the predicted effect of AChE inhibitors on cognition in Alzheimer's disease? (1)
Explain your answer. (1)
Improvement in cognitive function
They prevent ACh degradation and increase ACh levels in the synapse
183
How are irreversible AChE inhibitors thought to affect cognition? (1)
Probably no effect because they are toxic and would kill you
184
What effect would you predict AChR antagonists to have on cognition? (1)
Explain your answer. (1)
Produce cognitive/memory deficits similar to AD
Because they block the effects of ACh at receptors
185
Give two examples of AChR antagonists which could be used to produce animal models of Alzheimer's disease and cognitive decline. (2)
Scopolamine
Atropine
186
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)
For peripheral cholinergic issues
eg. urinary incontinence
187
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 ........................
sustained attention
excitatory ACh neurotransmission
188
Briefly describe a vigilance task which could be used to investigate the role of ACh in cognition. (3)
- 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
Describe the expected effect of scopolamine on vigilance task performance. (1)
Impaired performance
(slower responses and more errors)
190
Describe the expected effect of nicotine on vigilance task performance. (1)
Improved task performance
(faster responses and less errors)
191
Describe how the Y maze could be used to screen for the effects of Alzheimer's drugs. (3)
- Y maze assesses cognition and memory
- Use scopolamine model of cognitive impairment
- Test drugs for reversal of scopolamine-induced cognitive deficits
192
Describe how cholinergic neurotransmission may be associated with schizophrenia. (2)
Mutations in nicotinic a7 receptor increases chance of developing schizophrenia
Smoking unusually prevalent in schizophrenia, is this to reverse cognitive deficits?
193
Describe how cholinergic neurotransmission may be associated with Parkinson's Disease. (1)
Dopaminergic activity is heavily regulated by both muscarinic and nicotinic receptor activity
194
Describe how cholinergic neurotransmission may be associated with epilepsy. (1)
Mutations in nicotinic receptors associated with autosomal dominant nocturnal frontal lobe epilepsy
195
Describe how cholinergic neurotransmission may be associated with addiction. (2)
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
Describe how cholinergic neurotransmission may be associated with Alzheimer's disease. (2)
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
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)
Differences in expression profiles between subtypes (ie. different subtypes are expressed in different brain regions)
