Synapses and neurotransmitters Flashcards
(188 cards)
1
Q
What is a synapse?
A
A junction between 2 neurones allowing signals to pass from one to the other
2
Q
What is synaptic transmission?
A
The process of signalling via synapses
3
Q
What is the evidence for the existence of neurones? (3)
A
- Golgi stain
- Physiological evidence from reflex studies
- Electron microscopy
4
Q
What are the 2 kinds of synapses?
A
- Chemical
- Electrical
5
Q
What are electrical synapses?
A
Gap junctions made of connexins which allow current to flow directly between neurones (diffusion)
6
Q
How can you test for an electrical synapse? (3)
A
- Inject dye into a cell, will diffuse straight into the adjacent cell via the gap junction
- Stimulate a neurone, record the depolarisation and hyperpolarisation from the adjacent cell
- Connexin gene deletion
7
Q
What are electrical synapses good for? (2)
A
- Fast communication
- Synchronising neurones
8
Q
What was the first evidence for chemical synapses?
A
- Loewi’s experiment
- Stimulate Vagus nerve, remove fluid, add to recipient heart
- Heart rate slows
- Demonstrates that electrical signalling is converted to a chemical signal
9
Q
What are the steps of chemical synaptic transmission? (5)
A
- Package neurotransmitter in vesicles at the pre-synaptic terminal
- Action potential depolarisation causes opening of Ca2+ channels
- Ca2+ influx causes vesicles to fuse with the membrane and release neurotransmitter
- Neurotransmitter diffuses across synaptic cleft and activates receptors on post-synaptic membrane
- Neurotransmitter removed from synaptic cleft
10
Q
What are the 2 types of synaptic vesicles?
A
- Synaptic vesicles
- Dense-core secretory granules
11
Q
What is stored in synaptic vesicles?
A
Small molecule neurotransmitters
12
Q
What is stored in dense-core secretory granules?
A
Peptide neurotransmitters
13
Q
How are synaptic vesicles filled?
A
Filled by transporter proteins at the presynaptic terminal
14
Q
How are dense-core secretory granules filled?
A
Created and filled by the ER/Golgi secretory apparatus
15
Q
What happens to synaptic vesicles once they have released their cargo?
A
Recycled by endocytosis
16
Q
What happens to dense-core secretory granules once they have released their cargo?
A
Not recycled, single use
17
Q
What is synaptotagmin?
A
Ca2+ binding protein on vesicles
18
Q
What are the 2 types of SNAREs?
A
- v-SNAREs (vesicle)
- t-SNAREs (target)
19
Q
How does Ca2+ cause vesicle fusion?
A
- Ca2+ binds to synaptotagmin causing a conformational change
- Causes the SNAREs to join together and forces the vesicle to fuse with the membrane
20
Q
Which toxins target SNAREs? (2)
A
- Botulinum toxin
- Tetanus toxin
21
Q
What receptors can neurotransmitters bind to on the postsynaptic neurone?
A
- Ionotropic (ligand-gated ion channel)
- Metabotropic (G-protein coupled receptor)
22
Q
How can neurotransmitters be removed from the synaptic cleft? (3)
A
- Diffuse away
- Taken up into presynaptic neuron/glial cell and recycled
- Destroyed by enzymes in the synaptic cleft
23
Q
Which direction do signals pass in electrical synapses?
A
Both directions
24
Q
Which direction do signals pass in chemical synapses?
A
One direction
25
Which kind of synapse has faster signal transmission?
Electrical
26
Which kind of synapse can have more complicated downstream modulations/transformations?
Chemical
27
Do motor neuron action potentials always cause muscle cell action potentials?
Yes
28
Which neurotransmitter is used at neuromuscular junctions?
Acetylcholine (cholinergic)
29
What allows the neuromuscular junction to be so efficient? (3)
- Large number of active zones on presynaptic membrane
- Junctional folds on postsynaptic membrane
- Junctional folds directly opposite active zones
30
What are junctional folds?
Folds in the postsynaptic membrane of NMJ filled with neurotransmitter receptors
31
What proved the existence of vesicles?
- Stimulation of motor neurone caused endplate potentials which were integer multiples of spontaneous motor endplate potentials
- Concluded that neurones release discrete packages of neurotransmitter containing a set amount
- Spontaneous potential occurs when one vesicle accidentally fuses and releases its cargo
32
What is the criteria for a neurotransmitter? (4)
- Present in presynaptic terminals
- Released in response to stimulation
- Acts on the postsynaptic neuron
- Blocking the neurotransmitter prevents synaptic transmission
33
How could you determine if a molecule is acting as a neurotransmitter?
- Immunostaining to determine its presence, presence of enzymes to make it/transporter proteins to store it
- Collect the fluid around neurones after stimulation and analyse
- Test if the molecule mimics the effect of stimulating the cell
- Use drugs/delete genes/receptors to block the neurotransmitter
34
What are the 3 types of neurotransmitters?
- Amino acids (small molecules)
- Amines (small molecules)
- Peptides
35
How are amino acid neurotransmitters stored?
Synaptic vesicles
36
How are amine neurotransmitters stored?
Synaptic vesicles
37
How are peptide neurotransmitters stored?
Dense-core secretory granules
38
Which neurotransmitters are small molecules?
Amino acids and amines
39
Which receptors can small molecule neurotransmitters act on? (2)
- Ionotropic
| - Metabotropic
40
Which receptors can peptide neurotransmitters act on?
Metabotropic only
41
What is co-transmission?
When a peptide-releasing neuron also releases a small molecule transmitter at the same time, called the co-transmitter
42
What kind of neurotransmitter is glutamate?
Amino acid (small molecule)
43
What is the most common excitatory neurotransmitter in the CNS?
Glutamate
44
Which 3 ionotropic receptors does glutamate act on?
- AMPA receptor
- NMDA receptor
- Kainate receptor
45
How is glutamate action terminated?
Transporter proteins take up glutamate into the presynaptic terminal and glia
46
What happens when glutamate binds to AMPA receptors?
- Channel opens
- Allows Na+ into neuron and K+ out
- Causes an EPSP
47
What kind of receptor are AMPA receptors?
Ionotropic
48
What binds to AMPA receptors?
Glutamate
49
Which ions can pass through AMPA receptors? (2)
- Na+
| - K+
50
Which ions can pass through NMDA receptors? (3)
- Na+
- K+
- Ca2+
51
What binds to NMDA receptors?
Glutamate
52
What kind of receptor are NMDA receptors?
Ionotropic
53
What makes NMDA receptors different from AMPA receptors?
- NMDA receptors allow Ca2+ in but AMPA don't
| - NMDA receptors are blocked with Mg2+ when the neuron is at resting potential
54
Why is glutamate binding not enough to open NMDA receptors?
They are blocked with Mg2+ which is attracted to the negative inside of the neuron when at resting potential
55
How are NMDA receptors opened?
- Depolarisation of the neuron removes the voltage-dependent Mg2+ block (becomes more positive so repels)
- Glutamate binding can open the channel when the neuron is depolarised and the Mg2+ has been removed
56
How do NMDA receptors act as a coincidence detector?
They are dual-gated which means they are only opened when the neuron is activated right after already being activated
57
How many subunits do AMPA and NMDA receptors have?
4
58
Which metabotropic receptors does glutamate act on?
mGluR1, mGluR2 etc.
59
How can glutamate also be inhibitory?
Can act via an inhibitory metabotropic receptor
60
Is glutamate excitatory or inhibitory?
Excitatory
61
Is GABA excitatory or inhibitory?
Inhibitory
62
What kind of neurotransmitter is GABA?
Amino acid
| Not used to synthesis proteins
63
How is GABA made?
Synthesised from glutamate
64
Which enzyme converts glutamate to GABA?
Glutamic acid decarboxylase (GAD)
65
How is GABA action terminated?
Transporter proteins take up GABA into the presynaptic terminal and glia
66
Which ionotropic receptor does GABA act on?
GABAa receptor
67
Which ion can pass through GABAa receptors?
Cl-
68
What happens when GABA binds to GABAa receptors?
- Cl- enters the neuron
| - Produces an IPSP
69
What can too little GABA cause?
Seizures
70
What can too much GABA cause?
Coma/loss of consciousness
71
How do drugs modulate the activity of GABAa receptors?
- Bind to an allosteric binding site
| - Need GABA to also bind in order to cause an effect
72
Which drugs can modulate the activity of GABAa receptors? (3)
- Ethanol
- Benzodiazepines
- Barbiturates
73
What is the effect of ethanol on GABAa receptors?
Enhances the effects of GABA
74
What are benzodiazepines used to treat?
Anxiety
75
What is the effect of benzodiazepines on GABAa receptors?
Enhances the effects of GABA
76
What are barbiturates used for?
- Sedatives (used to be sleeping pills)
| - Anti-convulsants
77
What is the effect of barbiturates on GABAa receptors?
Enhances the effects of GABA
78
Which metabotropic receptor does GABA act on?
GABAb
79
Is GABAa receptor ionotropic or metabotropic?
Ionotropic
80
Is GABAb receptor ionotropic or metabotropic?
Metabotropic
81
How can GABAb receptors have an autoinhibitory effect?
GABAergic neuron could have GABAb receptors on itself which inhibit further release of GABA from the synaptic terminal
82
What kind of neurotransmitter is glycine?
Amino acid (small molecule)
83
Is glycine inhibitory or excitatory? (2)
- Can act like GABA on Cl- channels to be inhibitory (mainly inhibitory)
- Can bind to NMDA glutamate receptors to be excitatory
84
What happens when Cl- channels on a neurone are opened?
Membrane potential moves closer to the Nernst potential for Cl- (same with any ion)
85
How could a GABAergic neuron inhibit a neuron presynaptically?
- Release GABA which binds to GABAb receptors
- Causes a signalling cascade which results in Ca2+ channels on the neuron closing so vesicles can't fuse with the membrane and release neurotransmitter
86
Which enzyme is involved in the production of acetylcholine?
Choline acetyltransferase (ChAT)
87
How is acetylcholine made?
- Acetyl CoA plus choline
| - Catalysed by choline acetyltransferase (ChAT)
88
Where is choline acetyltransferase (ChAT) located?
In the cytoplasm of the presynaptic cholinergic neuron
89
What kind of neurotransmitter is ACh?
Small molecule
90
How is ACh stored in neurones?
Synaptic vesicles
91
How is ACh action terminated? (2)
- Destroyed in the synaptic cleft by acetylcholinesterase (AChE)
- Choline taken up again into presynaptic neurone via choline transporter and recycled
92
What is ACh broken down into by acetylcholinesterase?
Acetic acid and choline
93
Where does acetyl CoA come from?
Respiration
94
What are ionotropic ACh receptors called?
Nicotinic receptors
95
What are metabotropic ACh receptors called?
Muscarinic receptors
96
Where are nicotinic receptors found in the body? (2)
- Neuromuscular junction (NMJ)
| - CNS
97
What is an agonist for nicotinic receptors apart from ACh?
Nicotine
98
What is an antagonist for nicotinic receptors?
Curare
99
What happens when ACh binds to nicotinic receptors?
- Channel opens
| - Ions flow through to depolarise the neurone
100
What is an agonist for muscarinic receptors apart from ACh?
Muscarine
101
What is an antagonist for muscarinic receptors?
Atropine
102
Where are muscarinic receptors found in the body? (2)
- CNS
| - Autonomic nervous system
103
Which muscarinic receptors are excitatory? (3)
- M1
- M3
- M5
104
Which G protein are receptors M1, M3 and M5 coupled with?
Gq (excitatory)
105
Which muscarinic receptors are inhibitory? (2)
- M2
| - M4
106
Which G proteins are receptors M2 and M4 coupled with?
Gi/o (inhibitory)
107
Does the brain have more nicotinic or muscarinic receptors?
Muscarinic
108
Which ACh receptors are in the NMJ?
Nicotinic
109
Which drugs block ACh release? (2)
- Botulinum toxin
| - Black widow spider venom
110
Which drugs inhibit acetylcholinesterase? (3)
- Nerve gas
- Organophosphate pesticides
- Alzheimer's treatments
111
Which drugs activate ACh receptors? (2)
- Nicotine/muscarine
| - Neonicotinoid pesticides
112
Which drugs block ACh receptors?
- Nicotinic: curare, alpha-bungarotoxin
| - Muscarinic: atropine
113
Which neurotransmitters are catecholamines? (3)
- Dopamine
- Noradrenaline/norepinephrine
- Adrenaline/epinephrine
114
Which molecule is dopamine made from?
L-dopa
115
Which molecule is noradrenaline made from?
Dopamine
116
Which molecule is adrenaline made from?
Noradrenaline
117
Which neurotransmitters are monoamines? (4)
- Dopamine (catecholamine)
- Noradrenaline/norepinephrine (catecholamine)
- Adrenaline/epinephrine (catecholamine)
- Serotonin
118
What is serotonin abbreviated to?
5-HT (5-hydroxytryptamine)
119
Which molecule is serotonin made from?
Tryptophan (amino acid)
120
How are monoamines stored?
Packaged into synaptic vesicles by vesicular monoamine transporters (VMAT)
121
How is the action of monoamines terminated?
Reuptake transporters take them back up into the presynaptic neurone
122
Which enzyme destroys monoamines?
Monoamine oxidase (MAO)
123
Where is monoamine oxidase (MAO) located?
Presynaptic cell
124
Which enzyme destroys catecholamines?
Catechol-O-methyltransferase (COMT)
125
Where is catechol-O-methyltransferase (COMT) located?
Postsynaptic cell
126
Which type of receptors do monoamines mostly activate?
Metabotropic
127
What are the receptors for dopamine?
- D1 like: D1, D5
| - D2 like: D2, D3, D4
128
What are the receptors for adrenaline/epinephrine and noradrenaline/norepinephrine?
Alpha/beta type adrenergic receptors
129
What kind of receptors are dopamine receptors?
Metabotropic (G-protein)
130
What kind of receptors are adrenergic receptors?
Metabotropic (G-protein)
131
How many types of serotonin receptors are there?
7
132
What kind of receptors are serotonin receptors?
All metabotropic except 1 which is a ligand-gated Na+/K+ channel
133
What are the 2 major functions of dopamine?
- Motor control
| - Reward
134
Where in the brain are the motor control dopaminergic neurons?
Substantia nigra
135
Where in the brain do motor control dopaminergic neurones in the substantia nigra send their axons to?
Striatum
136
What is the neural pathway which facilitates initiation of voluntary movement?
Nigrostriatal pathway
137
What does the nigrostriatal pathway do?
Facilitates initiation of voluntary movement
138
Which neurones die in Parkinson's disease?
Motor control dopaminergic neurones
139
Why can't you give dopamine to Parkinson's patients?
Doesn't cross the blood-brain barrier
140
Which molecule are the catecholamines made from?
Tyrosine (amino acid)
141
What is given to Parkinson's patients?
- L-Dopa
| - Monoamine oxidase inhibitors
142
Why is L-Dopa used to treat Parkinson's?
Precursor to dopamine which can cross the blood-brain barrier and converted to dopamine by dopaminergic neurones to increase dopamine action in the brain
143
Why are monoamine oxidase inhibitors used to treat Parkinson's?
Prevents the breakdown of dopamine in the presynaptic neurones to increase dopamine levels in the brain
144
Where in the brain are the reward dopaminergic neurons?
Ventral tegmental area (VTA)
145
Where in the brain do reward dopaminergic neurones in the VTA send their axons to? (2)
- Cortex
| - Limbic system
146
What is the neural pathway which mediates reward/motivation?
Mesolimbic pathway
147
What does the mesolimbic pathway do?
Mediates reward/motivation
148
Where are noradrenergic neurones located in the brain?
Locus coeruleus
149
Where in the brain do noradrenergic neurones project to?
Whole brain
150
What do noradrenergic neurones regulate?
- Arousal
| - E.g. sleep/wake/attention/pain/anxiety etc
151
Where in the brain are serotonergic neurones located?
Raphe nuceli
152
Where in the brain do serotonergic neurones project to?
Whole brain
153
What do serotonergic neurones regulate?
- Sleep/wake
| - Mood
154
What does cocaine do?
- Blocks the dopamine reuptake transporter to enhance dopamine signalling
- Rewarding
155
What do amphetamines do?
- Block storage of dopamine and norepinephrine in vesicles
| - Block reuptake of dopamine and norepinephrine
156
What are examples of amphetamines? (2)
- Crystal meth
| - Adderall
157
What is Adderall used to treat?
ADHD
158
How do antipsychotics work?
Block dopamine receptors
159
What is a side effect of antipsychotics?
Parkinson's-like symptoms
160
What are 3 classes of antidepressants?
- Tricyclics
- Selective serotonin reuptake inhibitors (SSRIs)
- Monoamine oxidase inhibitors
161
How do tricyclic antidepressants work?
Inhibit reuptake transporters of noradrenaline and serotonin
162
What do antidepressants do?
Increase serotonin levels
163
How do SSRIs work?
Inhibit serotonin reuptake transporters
164
What are examples of SSRIs? (2)
- Fluoxetine
| - Prozac
165
What is Fluoxetine?
SSRI antidepressant
166
What is Prozac?
SSRI antidepressant
167
What are endorphins?
Opioid peptide neurotransmitters
168
What kind of receptors are opioid receptors?
Metabotropic (G-protein)
169
What do opioid peptide neurotransmitters regulate? (3)
- Pain (main)
- Coughing
- GI tract function (digestion side effects)
170
How is ATP used as a neurotransmitter?
Co-transmitter
171
What are the 2 classes of ATP receptors?
- P2X2
| - P2Y2
172
What kind of receptors are P2X2 ATP receptors?
Ionotropic
173
What kind of receptors are P2Y2 ATP receptors?
Metabotropic
174
How are endocannabinoid neurotransmitters stored?
- Not stored
| - Lipid soluble so diffuse across the membrane
175
How are endocannabinoid neurotransmitters released?
- Ca2+ activates the enzymes which make endocannabinoids
| - Endocannabinoids made on demand and diffuse across the membrane
176
What is retrograde signalling?
Endocannabinoids can signal from post to presynaptic neurone
177
Which kind of receptors do endocannabinoids activate?
Metabotropic
178
How is nitric oxide neurotransmitter stored?
- Not stored, synthesised on demand
| - Gas so can diffuse across membranes
179
What is the target of nitric oxide?
Soluble guanylate cyclase inside cells
180
What does guanylate cyclase do?
Converts GTP to cGMP
181
Which enzyme converts tyrosine to L-Dopa?
Tyrosine hydroxylase
182
What does tyrosine hydroxylase do?
Converts tyrosine to L-Dopa
183
Which enzyme converts L-Dopa to dopamine?
Dopa decarboxylase
184
What does dopa decarboxylase do?
Converts L-Dopa to dopamine
185
Which enzyme converts dopamine to noradrenaline?
Dopamine beta-hydroxylase
186
What does dopamine beta-hydroxylase do?
Converts dopamine to noradrenaline
187
Which enzyme converts noradrenaline to adrenaline?
Phentolamine N-methyltransferase (PNMT)
188
What does phentolamine N-methyltransferase do?
Converts noradrenaline to adrenaline
