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Neuroscience > Synapses and neurotransmitters > Flashcards

Synapses and neurotransmitters Flashcards

1
Q

What is a synapse?

A

A junction between 2 neurones allowing signals to pass from one to the other

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2
Q

What is synaptic transmission?

A

The process of signalling via synapses

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3
Q

What is the evidence for the existence of neurones? (3)

A
  • Golgi stain
  • Physiological evidence from reflex studies
  • Electron microscopy
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4
Q

What are the 2 kinds of synapses?

A
  • Chemical

- Electrical

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5
Q

What are electrical synapses?

A

Gap junctions made of connexins which allow current to flow directly between neurones (diffusion)

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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
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7
Q

What are electrical synapses good for? (2)

A
  • Fast communication

- Synchronising neurones

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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
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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
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10
Q

What are the 2 types of synaptic vesicles?

A
  • Synaptic vesicles

- Dense-core secretory granules

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11
Q

What is stored in synaptic vesicles?

A

Small molecule neurotransmitters

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12
Q

What is stored in dense-core secretory granules?

A

Peptide neurotransmitters

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13
Q

How are synaptic vesicles filled?

A

Filled by transporter proteins at the presynaptic terminal

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14
Q

How are dense-core secretory granules filled?

A

Created and filled by the ER/Golgi secretory apparatus

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15
Q

What happens to synaptic vesicles once they have released their cargo?

A

Recycled by endocytosis

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16
Q

What happens to dense-core secretory granules once they have released their cargo?

A

Not recycled, single use

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17
Q

What is synaptotagmin?

A

Ca2+ binding protein on vesicles

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18
Q

What are the 2 types of SNAREs?

A
  • v-SNAREs (vesicle)

- t-SNAREs (target)

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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
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20
Q

Which toxins target SNAREs? (2)

A
  • Botulinum toxin

- Tetanus toxin

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21
Q

What receptors can neurotransmitters bind to on the postsynaptic neurone?

A
  • Ionotropic (ligand-gated ion channel)

- Metabotropic (G-protein coupled receptor)

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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
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23
Q

Which direction do signals pass in electrical synapses?

A

Both directions

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24
Q

Which direction do signals pass in chemical synapses?

A

One direction

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25
Q

Which kind of synapse has faster signal transmission?

A

Electrical

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26
Q

Which kind of synapse can have more complicated downstream modulations/transformations?

A

Chemical

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27
Q

Do motor neuron action potentials always cause muscle cell action potentials?

A

Yes

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28
Q

Which neurotransmitter is used at neuromuscular junctions?

A

Acetylcholine (cholinergic)

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29
Q

What allows the neuromuscular junction to be so efficient? (3)

A
  • Large number of active zones on presynaptic membrane
  • Junctional folds on postsynaptic membrane
  • Junctional folds directly opposite active zones
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30
Q

What are junctional folds?

A

Folds in the postsynaptic membrane of NMJ filled with neurotransmitter receptors

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31
Q

What proved the existence of vesicles?

A
  • 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
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32
Q

What is the criteria for a neurotransmitter? (4)

A
  • Present in presynaptic terminals
  • Released in response to stimulation
  • Acts on the postsynaptic neuron
  • Blocking the neurotransmitter prevents synaptic transmission
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33
Q

How could you determine if a molecule is acting as a neurotransmitter?

A
  • 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
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34
Q

What are the 3 types of neurotransmitters?

A
  • Amino acids (small molecules)
  • Amines (small molecules)
  • Peptides
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35
Q

How are amino acid neurotransmitters stored?

A

Synaptic vesicles

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36
Q

How are amine neurotransmitters stored?

A

Synaptic vesicles

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37
Q

How are peptide neurotransmitters stored?

A

Dense-core secretory granules

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38
Q

Which neurotransmitters are small molecules?

A

Amino acids and amines

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39
Q

Which receptors can small molecule neurotransmitters act on? (2)

A
  • Ionotropic

- Metabotropic

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40
Q

Which receptors can peptide neurotransmitters act on?

A

Metabotropic only

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41
Q

What is co-transmission?

A

When a peptide-releasing neuron also releases a small molecule transmitter at the same time, called the co-transmitter

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42
Q

What kind of neurotransmitter is glutamate?

A

Amino acid (small molecule)

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43
Q

What is the most common excitatory neurotransmitter in the CNS?

A

Glutamate

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44
Q

Which 3 ionotropic receptors does glutamate act on?

A
  • AMPA receptor
  • NMDA receptor
  • Kainate receptor
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45
Q

How is glutamate action terminated?

A

Transporter proteins take up glutamate into the presynaptic terminal and glia

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46
Q

What happens when glutamate binds to AMPA receptors?

A
  • Channel opens
  • Allows Na+ into neuron and K+ out
  • Causes an EPSP
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47
Q

What kind of receptor are AMPA receptors?

A

Ionotropic

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48
Q

What binds to AMPA receptors?

A

Glutamate

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49
Q

Which ions can pass through AMPA receptors? (2)

A
  • Na+

- K+

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50
Q

Which ions can pass through NMDA receptors? (3)

A
  • Na+
  • K+
  • Ca2+
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51
Q

What binds to NMDA receptors?

A

Glutamate

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52
Q

What kind of receptor are NMDA receptors?

A

Ionotropic

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53
Q

What makes NMDA receptors different from AMPA receptors?

A
  • NMDA receptors allow Ca2+ in but AMPA don’t

- NMDA receptors are blocked with Mg2+ when the neuron is at resting potential

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54
Q

Why is glutamate binding not enough to open NMDA receptors?

A

They are blocked with Mg2+ which is attracted to the negative inside of the neuron when at resting potential

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55
Q

How are NMDA receptors opened?

A
  • 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
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56
Q

How do NMDA receptors act as a coincidence detector?

A

They are dual-gated which means they are only opened when the neuron is activated right after already being activated

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57
Q

How many subunits do AMPA and NMDA receptors have?

A

4

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58
Q

Which metabotropic receptors does glutamate act on?

A

mGluR1, mGluR2 etc.

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59
Q

How can glutamate also be inhibitory?

A

Can act via an inhibitory metabotropic receptor

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60
Q

Is glutamate excitatory or inhibitory?

A

Excitatory

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61
Q

Is GABA excitatory or inhibitory?

A

Inhibitory

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62
Q

What kind of neurotransmitter is GABA?

A

Amino acid

Not used to synthesis proteins

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63
Q

How is GABA made?

A

Synthesised from glutamate

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64
Q

Which enzyme converts glutamate to GABA?

A

Glutamic acid decarboxylase (GAD)

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65
Q

How is GABA action terminated?

A

Transporter proteins take up GABA into the presynaptic terminal and glia

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66
Q

Which ionotropic receptor does GABA act on?

A

GABAa receptor

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67
Q

Which ion can pass through GABAa receptors?

A

Cl-

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68
Q

What happens when GABA binds to GABAa receptors?

A
  • Cl- enters the neuron

- Produces an IPSP

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69
Q

What can too little GABA cause?

A

Seizures

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70
Q

What can too much GABA cause?

A

Coma/loss of consciousness

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71
Q

How do drugs modulate the activity of GABAa receptors?

A
  • Bind to an allosteric binding site

- Need GABA to also bind in order to cause an effect

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72
Q

Which drugs can modulate the activity of GABAa receptors? (3)

A
  • Ethanol
  • Benzodiazepines
  • Barbiturates
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73
Q

What is the effect of ethanol on GABAa receptors?

A

Enhances the effects of GABA

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74
Q

What are benzodiazepines used to treat?

A

Anxiety

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75
Q

What is the effect of benzodiazepines on GABAa receptors?

A

Enhances the effects of GABA

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76
Q

What are barbiturates used for?

A
  • Sedatives (used to be sleeping pills)

- Anti-convulsants

77
Q

What is the effect of barbiturates on GABAa receptors?

A

Enhances the effects of GABA

78
Q

Which metabotropic receptor does GABA act on?

A

GABAb

79
Q

Is GABAa receptor ionotropic or metabotropic?

A

Ionotropic

80
Q

Is GABAb receptor ionotropic or metabotropic?

A

Metabotropic

81
Q

How can GABAb receptors have an autoinhibitory effect?

A

GABAergic neuron could have GABAb receptors on itself which inhibit further release of GABA from the synaptic terminal

82
Q

What kind of neurotransmitter is glycine?

A

Amino acid (small molecule)

83
Q

Is glycine inhibitory or excitatory? (2)

A
  • Can act like GABA on Cl- channels to be inhibitory (mainly inhibitory)
  • Can bind to NMDA glutamate receptors to be excitatory
84
Q

What happens when Cl- channels on a neurone are opened?

A

Membrane potential moves closer to the Nernst potential for Cl- (same with any ion)

85
Q

How could a GABAergic neuron inhibit a neuron presynaptically?

A
  • 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
Q

Which enzyme is involved in the production of acetylcholine?

A

Choline acetyltransferase (ChAT)

87
Q

How is acetylcholine made?

A
  • Acetyl CoA plus choline

- Catalysed by choline acetyltransferase (ChAT)

88
Q

Where is choline acetyltransferase (ChAT) located?

A

In the cytoplasm of the presynaptic cholinergic neuron

89
Q

What kind of neurotransmitter is ACh?

A

Small molecule

90
Q

How is ACh stored in neurones?

A

Synaptic vesicles

91
Q

How is ACh action terminated? (2)

A
  • Destroyed in the synaptic cleft by acetylcholinesterase (AChE)
  • Choline taken up again into presynaptic neurone via choline transporter and recycled
92
Q

What is ACh broken down into by acetylcholinesterase?

A

Acetic acid and choline

93
Q

Where does acetyl CoA come from?

A

Respiration

94
Q

What are ionotropic ACh receptors called?

A

Nicotinic receptors

95
Q

What are metabotropic ACh receptors called?

A

Muscarinic receptors

96
Q

Where are nicotinic receptors found in the body? (2)

A
  • Neuromuscular junction (NMJ)

- CNS

97
Q

What is an agonist for nicotinic receptors apart from ACh?

A

Nicotine

98
Q

What is an antagonist for nicotinic receptors?

A

Curare

99
Q

What happens when ACh binds to nicotinic receptors?

A
  • Channel opens

- Ions flow through to depolarise the neurone

100
Q

What is an agonist for muscarinic receptors apart from ACh?

A

Muscarine

101
Q

What is an antagonist for muscarinic receptors?

A

Atropine

102
Q

Where are muscarinic receptors found in the body? (2)

A
  • CNS

- Autonomic nervous system

103
Q

Which muscarinic receptors are excitatory? (3)

A
  • M1
  • M3
  • M5
104
Q

Which G protein are receptors M1, M3 and M5 coupled with?

A

Gq (excitatory)

105
Q

Which muscarinic receptors are inhibitory? (2)

A
  • M2

- M4

106
Q

Which G proteins are receptors M2 and M4 coupled with?

A

Gi/o (inhibitory)

107
Q

Does the brain have more nicotinic or muscarinic receptors?

A

Muscarinic

108
Q

Which ACh receptors are in the NMJ?

A

Nicotinic

109
Q

Which drugs block ACh release? (2)

A
  • Botulinum toxin

- Black widow spider venom

110
Q

Which drugs inhibit acetylcholinesterase? (3)

A
  • Nerve gas
  • Organophosphate pesticides
  • Alzheimer’s treatments
111
Q

Which drugs activate ACh receptors? (2)

A
  • Nicotine/muscarine

- Neonicotinoid pesticides

112
Q

Which drugs block ACh receptors?

A
  • Nicotinic: curare, alpha-bungarotoxin

- Muscarinic: atropine

113
Q

Which neurotransmitters are catecholamines? (3)

A
  • Dopamine
  • Noradrenaline/norepinephrine
  • Adrenaline/epinephrine
114
Q

Which molecule is dopamine made from?

A

L-dopa

115
Q

Which molecule is noradrenaline made from?

A

Dopamine

116
Q

Which molecule is adrenaline made from?

A

Noradrenaline

117
Q

Which neurotransmitters are monoamines? (4)

A
  • Dopamine (catecholamine)
  • Noradrenaline/norepinephrine (catecholamine)
  • Adrenaline/epinephrine (catecholamine)
  • Serotonin
118
Q

What is serotonin abbreviated to?

A

5-HT (5-hydroxytryptamine)

119
Q

Which molecule is serotonin made from?

A

Tryptophan (amino acid)

120
Q

How are monoamines stored?

A

Packaged into synaptic vesicles by vesicular monoamine transporters (VMAT)

121
Q

How is the action of monoamines terminated?

A

Reuptake transporters take them back up into the presynaptic neurone

122
Q

Which enzyme destroys monoamines?

A

Monoamine oxidase (MAO)

123
Q

Where is monoamine oxidase (MAO) located?

A

Presynaptic cell

124
Q

Which enzyme destroys catecholamines?

A

Catechol-O-methyltransferase (COMT)

125
Q

Where is catechol-O-methyltransferase (COMT) located?

A

Postsynaptic cell

126
Q

Which type of receptors do monoamines mostly activate?

A

Metabotropic

127
Q

What are the receptors for dopamine?

A
  • D1 like: D1, D5

- D2 like: D2, D3, D4

128
Q

What are the receptors for adrenaline/epinephrine and noradrenaline/norepinephrine?

A

Alpha/beta type adrenergic receptors

129
Q

What kind of receptors are dopamine receptors?

A

Metabotropic (G-protein)

130
Q

What kind of receptors are adrenergic receptors?

A

Metabotropic (G-protein)

131
Q

How many types of serotonin receptors are there?

A

7

132
Q

What kind of receptors are serotonin receptors?

A

All metabotropic except 1 which is a ligand-gated Na+/K+ channel

133
Q

What are the 2 major functions of dopamine?

A
  • Motor control

- Reward

134
Q

Where in the brain are the motor control dopaminergic neurons?

A

Substantia nigra

135
Q

Where in the brain do motor control dopaminergic neurones in the substantia nigra send their axons to?

A

Striatum

136
Q

What is the neural pathway which facilitates initiation of voluntary movement?

A

Nigrostriatal pathway

137
Q

What does the nigrostriatal pathway do?

A

Facilitates initiation of voluntary movement

138
Q

Which neurones die in Parkinson’s disease?

A

Motor control dopaminergic neurones

139
Q

Why can’t you give dopamine to Parkinson’s patients?

A

Doesn’t cross the blood-brain barrier

140
Q

Which molecule are the catecholamines made from?

A

Tyrosine (amino acid)

141
Q

What is given to Parkinson’s patients?

A
  • L-Dopa

- Monoamine oxidase inhibitors

142
Q

Why is L-Dopa used to treat Parkinson’s?

A

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
Q

Why are monoamine oxidase inhibitors used to treat Parkinson’s?

A

Prevents the breakdown of dopamine in the presynaptic neurones to increase dopamine levels in the brain

144
Q

Where in the brain are the reward dopaminergic neurons?

A

Ventral tegmental area (VTA)

145
Q

Where in the brain do reward dopaminergic neurones in the VTA send their axons to? (2)

A
  • Cortex

- Limbic system

146
Q

What is the neural pathway which mediates reward/motivation?

A

Mesolimbic pathway

147
Q

What does the mesolimbic pathway do?

A

Mediates reward/motivation

148
Q

Where are noradrenergic neurones located in the brain?

A

Locus coeruleus

149
Q

Where in the brain do noradrenergic neurones project to?

A

Whole brain

150
Q

What do noradrenergic neurones regulate?

A
  • Arousal

- E.g. sleep/wake/attention/pain/anxiety etc

151
Q

Where in the brain are serotonergic neurones located?

A

Raphe nuceli

152
Q

Where in the brain do serotonergic neurones project to?

A

Whole brain

153
Q

What do serotonergic neurones regulate?

A
  • Sleep/wake

- Mood

154
Q

What does cocaine do?

A
  • Blocks the dopamine reuptake transporter to enhance dopamine signalling
  • Rewarding
155
Q

What do amphetamines do?

A
  • Block storage of dopamine and norepinephrine in vesicles

- Block reuptake of dopamine and norepinephrine

156
Q

What are examples of amphetamines? (2)

A
  • Crystal meth

- Adderall

157
Q

What is Adderall used to treat?

A

ADHD

158
Q

How do antipsychotics work?

A

Block dopamine receptors

159
Q

What is a side effect of antipsychotics?

A

Parkinson’s-like symptoms

160
Q

What are 3 classes of antidepressants?

A
  • Tricyclics
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Monoamine oxidase inhibitors
161
Q

How do tricyclic antidepressants work?

A

Inhibit reuptake transporters of noradrenaline and serotonin

162
Q

What do antidepressants do?

A

Increase serotonin levels

163
Q

How do SSRIs work?

A

Inhibit serotonin reuptake transporters

164
Q

What are examples of SSRIs? (2)

A
  • Fluoxetine

- Prozac

165
Q

What is Fluoxetine?

A

SSRI antidepressant

166
Q

What is Prozac?

A

SSRI antidepressant

167
Q

What are endorphins?

A

Opioid peptide neurotransmitters

168
Q

What kind of receptors are opioid receptors?

A

Metabotropic (G-protein)

169
Q

What do opioid peptide neurotransmitters regulate? (3)

A
  • Pain (main)
  • Coughing
  • GI tract function (digestion side effects)
170
Q

How is ATP used as a neurotransmitter?

A

Co-transmitter

171
Q

What are the 2 classes of ATP receptors?

A
  • P2X2

- P2Y2

172
Q

What kind of receptors are P2X2 ATP receptors?

A

Ionotropic

173
Q

What kind of receptors are P2Y2 ATP receptors?

A

Metabotropic

174
Q

How are endocannabinoid neurotransmitters stored?

A
  • Not stored

- Lipid soluble so diffuse across the membrane

175
Q

How are endocannabinoid neurotransmitters released?

A
  • Ca2+ activates the enzymes which make endocannabinoids

- Endocannabinoids made on demand and diffuse across the membrane

176
Q

What is retrograde signalling?

A

Endocannabinoids can signal from post to presynaptic neurone

177
Q

Which kind of receptors do endocannabinoids activate?

A

Metabotropic

178
Q

How is nitric oxide neurotransmitter stored?

A
  • Not stored, synthesised on demand

- Gas so can diffuse across membranes

179
Q

What is the target of nitric oxide?

A

Soluble guanylate cyclase inside cells

180
Q

What does guanylate cyclase do?

A

Converts GTP to cGMP

181
Q

Which enzyme converts tyrosine to L-Dopa?

A

Tyrosine hydroxylase

182
Q

What does tyrosine hydroxylase do?

A

Converts tyrosine to L-Dopa

183
Q

Which enzyme converts L-Dopa to dopamine?

A

Dopa decarboxylase

184
Q

What does dopa decarboxylase do?

A

Converts L-Dopa to dopamine

185
Q

Which enzyme converts dopamine to noradrenaline?

A

Dopamine beta-hydroxylase

186
Q

What does dopamine beta-hydroxylase do?

A

Converts dopamine to noradrenaline

187
Q

Which enzyme converts noradrenaline to adrenaline?

A

Phentolamine N-methyltransferase (PNMT)

188
Q

What does phentolamine N-methyltransferase do?

A

Converts noradrenaline to adrenaline

Neuroscience (18 decks)

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