Neurotransmitters and synaptic transmission

Question 1

Catecholamines are important neurotransmitters linked with many different functions. How
are they synthesized? Start with the precursor and end with the final product (each compound in the correct order). State also the name and role of the rate-limiting enzyme.

Answer 1

Tyrosine -> DOPA -> Dopamine -> Noradrenaline -> Adrenaline

Rate-limiting enzyme: Tyrosine hydroxylase

Question 2

How is glutamate inactivated?

Answer 2

It is (primarily) taken up into adjacent astrocytes in which it is converted to glutamine.

Question 3

How is acetylcholine inactivated?

Answer 3

It is broken down by acetylcholinesterase into choline and acetate, choline is then taken
up in the nerve terminal.

Question 4

Which ion(s) can pass NMDA receptors?

Answer 4

Sodium, Potassium and Calcium.

Question 5

Neurons use a variety of neurotransmitters. State which neurotransmitter is used by each of the following neuron types:

a) Purkinje cells in the cerebellum:
b) Alpha-motor neurons in the spinal cord:
c) Medium spiny neurons in striatum:
d) Muscle spindle afferents (Ia afferents):
e) Postganglionic sympathetic neurons:
f) Nigrostriatal neurons:

Answer 5

a) Purkinje cells in the cerebellum: GABA
b) Alpha-motor neurons in the spinal cord: Acetylcholine
c) Medium spiny neurons in the striatum: GABA
d) Muscle spindle afferents (Ia afferents): Glutamate
e) Postganglionic sympathetic neurons: Noradrenaline
f) Nigrostriatal neurons: Dopamine

Question 6

Long-term potentiation (LTP) and long-term depression (LTD) can be induced in hippocampal synapses as well as in many other synapses.

a) Which type of stimulus is effective for inducing LTP?
b) Which type of stimulus is effective for inducing LTD?

Answer 6

2a: Brief, high-frequency stimulation (e.g. 100 Hz for 1 s).
2b: Long-lasting low-frequency stimulation (e.g. 1 Hz for 15 min)

Question 7

What characterizes glycine?

Answer 7

B) It is an inhibitory neurotransmitter

C) It occurs in (small) synaptic vesicles

Question 8

What is true about these neurotransmitters?
A) Dopamine does not activate ionotropic receptors
B) Serotonin does not activate ionotropic receptors
C) Glutamate does not activate ionotropic receptors
D) Glutamate does not activate metabotropic receptors

Answer 8

A) Dopamine does not activate ionotropic receptors

Question 9

What is true about neuropeptides?
A) Dopamine is a neuropeptide
B) Serotonin is not a neuropeptide
C) Enkephalin is not a neuropeptide
D) Cholecystokinin can not be stored in large dense cored vesicles

Answer 9

B) Serotonin is not a neuropeptide

Question 10

What is true about neurotransmitter inactivation?
A) Acetylcholine is inactivated by uptake
B) Glutamate is inactivated by uptake
C) Inhibitors of acetylcholine degradation can not be used to treat
myasthenia gravis
D) Inhibitors of acetylcholine degradation can be used to treat
Alzheimers disease

Answer 10

B) Glutamate is inactivated by uptake

D) Inhibitors of acetylcholine degradation can be used to treat Alzheimers disease

Question 11

What is true about neurotransmitter synthesis?
A) Glutamate is not a precursor of GABA
B) Glutamine is a precursor of glutamate
C) Choline is not a precursor of acetylcholine
D) Dopamine is a precursor of L-DOPA

Answer 11

B) Glutamine is a precursor of glutamate

Question 12

What is true about chemical synapses?

Answer 12

A) They contain synapsin
B) They contain Munc18
C) They contain actin
D) They contain protein kinases

Question 13

What is true about synaptic vesicles?
Which kinds exist?
Where are they recycled?
What do they depend on for membrane fusion?

Answer 13

A) Regular (small) synaptic vesicles are recycled in nerve terminals
B) Large dense cored vesicles are not recycled in nerve terminals
C) Fusion of large dense cored vesicles depend on SNARE
proteins
D) Fusion of (small) synaptic vesicles depend on SNARE
proteins

Question 14

Mention a type of strengthening that lasts for milliseconds to seconds and describe briefly the underlying mechanism

Answer 14

Facilitation.

accumulation of calcium in the presynaptic terminal during repetitive action potential stimulation.

Question 15

Mention a type of strengthening that lasts for up to a few hours and describe briefly the underlying mechanism

Answer 15

The early phase of long-term potentiation (LTP).

1. brief high-frequency trains of action potentials
2. opening of voltage-sensitive NMDA channels giving rise to calcium influx.
3. activation of kinases
4. insertion of more AMPA receptors in the postsynaptic membrane (by exocytosis)

Question 16

Mention a type of strengthening that lasts for days, weeks or even longer and describe briefly the underlying mechanism.

Answer 16

The late phase of long-term potentiation (LTP).
1. brief high-frequency trains of action potentials
2. opening of voltage-sensitive NMDA channels giving rise to calcium influx.
3. activation of kinases
4. activation of transcription factors (such as CREB)
5. increased expression of genes encoding synaptic proteins
Thereby synapses can be enlarged and/or new synapses can form.

Question 17

Mention a neuron type that uses acetylcholine as a neurotransmitter?

Answer 17

Motorneurons. Also correct are postganglionic parasympathetic neurons, striatal cholinergic interneurons and cholinergic basal forebrain neurons.

Question 18

In which type of vesicle is acetylcholine stored?

Answer 18

It is stored in synaptic vesicles (also called small synaptic vesicles, i.e. not in large dense-cored vesicles)

Question 19

On which two main types of postsynaptic receptor does acetylcholine act? Both the names and types of receptor are required.

Answer 19

Nicotinic receptors which are ligand-gated ion channels (=ionotropic receptors)

Muscarinic receptors are G-protein-coupled receptors (=metabotropic receptors).

Question 20

Inhibition of the inactivation of acetylcholine can be used clinically –which type of drug and/or which disease does it regard?

Answer 20

Acetylcholinesterase inhibitors (like neostigmine, rivastigmine and donepezil). They are used to treat myasthenia gravis, Alzheimer´s disease and glaucoma.

Question 21

Inhibition of the inactivation acetylcholine can also be used with deleterious effects in war or in terrorist attacks – by which compound and/or mechanism? Either a compound or a mechanism of action is sufficient.

Answer 21

Nerve gases/nerve agents:

Sarin, tabun and Novichok block acetylcholinesterase

Effect: fatal overactivation of acetylcholine receptors.

Atropine can be used as an antidote as it blocks muscarinic acetylcholine receptors.

Question 22

Which is the major inhibitory neurotransmitter in the brain?

Answer 22

GABA

Question 23

Describe how GABA is synthesized.

Answer 23

Location: synthesized in inhibitory nerve terminals

How: by conversion of glutamate by the enzyme glutamate decarboxylase (GAD).

Question 24

Which is the major neurotransmitter in the nigrostriatal and mesolimbic pathways?

Answer 24

Dopamine

Question 25

Poisoning by Botulinum toxins and Tetanus toxin gives rise to different symptoms.
How do these toxins act? How do the symptoms produced by the two toxins differ
and how can this be explained?

Answer 25

Both toxins act as proteases that specifically cleave SNARE proteins. In doing so they block the fusion
of synaptic vesicles with the plasma membrane and thereby neurotransmitter release from the affected nerve terminal.

Botulinum toxins give rise to flaccid paralysis (reduced muscle tone) as toxins are taken up into neuromuscular nerve terminals and act directly in the terminal they have been taken up into.

Tetanus toxin gives rise to muscle spasms (increased muscle tone) as the toxin is transported across synapses and is taken up into presynaptic
terminals of interneurons, reducing the release of inhibitory neurotransmitters, which causes the enhanced activity of the motor neurons.

Question 26

The SNARE proteins synaptobrevin, syntaxin and SNAP25 are critical for neurotransmitter release but they require additional proteins to mediate their function -
describe briefly the roles of complexin and synaptotagmin in the release process

Answer 26

1. Complexin acts prior to the fusion process. It binds to the partially formed SNARE complex “priming” it for release.
2. Synaptotagmin binds Ca2+, replacing complexin, and triggers the formation of a complete SNARE complex allowing fusion of the vesicle with the plasma membrane.

Question 27

There are two main classes of neurotransmitter – small molecule neurotransmitters and neuropeptides (”large”), respectively. Give two examples of each type and
describe where they are synthesized and where they are stored.

Answer 27

Small molecule neurotransmitters: For example glutamate, GABA, glycine acetylcholine, and monoamines like dopamine and serotonin. They are synthesized in nerve terminals and stored in (small) synaptic vesicles (SV) that are aggregated at
active zones. The monoamines can additionally be synthesized in cell bodies and stored in large dense-cored vesicles (LDV)

Neuropeptides: For example enkephalins, endorphins, NPY, substance P, somatostatin, cholecystokinin. They are synthesized in cell bodies and stored in large
dense-cored vesicles (LDV) that are located outside of the active zones.