Lecture 8: Presynaptic Processes

Question 1

What are neurotransmitters? What are they released into?

Answer 1

chemical signals released from presynaptic nerve terminals into the synaptic cleft

Question 2

How is a signal passed on from one neuron to the next?

Answer 2

release of one (or more) chemicals from the axon terminal -> these chemicals act on receptors of the target cell to temporarily change the properties of that cell i.e. change in membrane potential or conductance

Question 3

What are the criteria that must be met in order for a chemical to be considered a neurotransmitter?

Answer 3

synthesis: must be produced within a neuron
storage: must be found within a neuron
release: must be released when the neuron is depolarised
receptor: must act on a post-synaptic receptor and cause a biological effect
inactivation: there must be a mechanism for inactivation (uptake / degradation)
if applied on a post-synaptic membrane, it should have the same effect as when released by a neuron

Question 4

What are examples of classical (small molecule) neurotransmitters?

Answer 4

amino acids such as glutamate, GABA and glycine
monoamines such as noradrenaline, dopamine, adrenaline and serotonin
acetylcholine

Question 5

What are examples of non-classical (large peptide) neurotransmitters?

Answer 5

peptides such as substance P, somatostatin, enkephalin and kisspeptin
gases such as nitric oxide and carbon monoxide
lipids such as anandamide

Question 6

How are classical and non-classical neurotransmitters synthesised?

Answer 6

classical: uptake or enzymes

non-classical: protein synthesis

Question 7

How long is the duration of action for classical and non-classical neurotransmitters?

Answer 7

classical: fast and short

non-classical: slow and long

Question 8

What are the vesicles like for classical and non-classical neurotransmitters?

Answer 8

classical: small (filled by transporters)

non-classical: large (secreted proteins from RER)

Question 9

What is the sequence of events involved in neurotransmission?

Answer 9

NT synthesised and stored -> AP -> depolarisation and opening of VGCC -> Ca2+ influx -> vesicles fuse with presynaptic membrane -> NT released via exocytosis -> NT binds receptors on postsynaptic membrane -> postsynaptic channels open -> postsynaptic current causes EPSP or IPSP -> reuptake and / or breakdown of NT

Question 10

What do VGCCs couple?

Answer 10

couple membrane depolarisation to NT release

Ca2+ that enters binds to release proteins to cause vesicle fusion

Question 11

What are the different types of VGCCs?

Answer 11

N-type (Cav2.2) - classical blocker: conotoxin (cone snails)

P/Q (Cav2.1) - classic toxin agatoxin (spiders)

Question 12

How are neurotransmitters released and what is this known as?

Answer 12

NTs are released in packets and this is known as quantal release

Question 13

Neurotransmitters are released in packets. What does this determine?

Answer 13

determines the minimum size of a postsynaptic potential (EPSP or IPSP in neurons)

Question 14

What is an mEPP?

Answer 14

the change in the membrane potential of a muscle cell produced by a single quantum is called a miniature end-plate potential

Question 15

What is a quantum?

Answer 15

the amount of neurotransmitter in 1 vesicle

Question 16

How big is an mEPP? What implication does this have upon neurotransmitter release?

Answer 16

an mEPP is only about 1/100 the size of the end-plate potential (EPP) produced by electrical stimulation of the entire nerve innervating the muscle fibre
therefore, normal neurotransmission results from the release of many vesicles simultaneously

Question 17

What is the relationship of synaptic vesicle exocytosis and quantal transmitter release?

Answer 17

there is a 1:1 ratio between the number of vesicles fusing and the number of quanta being released

Question 18

What does low frequency stimulation lead to?

Answer 18

preferentially raises the Ca2+ concentration close to the membrane favouring the release of transmitter from small clear-core vesicles

Question 19

What does high frequency stimulation lead to?

Answer 19

more general increase in Ca2+ concentration causing the release of neuropeptides from large dense core vesicles as well as small molecule neurotransmitters

Question 20

What is the process of co-release?

Answer 20

both neurotransmitters are packaged into the same set of synaptic vesicles
when the presynaptic terminal is depolarized it causes the release of both neurotransmitters

Question 21

What is the process of co-transmission?

Answer 21

requires transmitters to be packaged into distinct synaptic vesicles with differential release mediated by differential Ca2+ sensitivity
alternatively, co-transmission can rely on spatial segregation of vesicle populations to different boutons to different synaptic targets

Question 22

What is the cytoplasmic surface of the vesicle membrane covered in?

Answer 22

densely covered in proteins which act at one or more steps in the synaptic vesicle cycle

Question 23

What is the role of synapsin?

Answer 23

may keep vesicles tethered within the reserve pool by crosslinking vesicles to each other and to actin filaments in the cytoskeleton

Question 24

What is the structure of a SNARE complex?

Answer 24

synaptobrevin (vesicular SNARE)
syntaxin (plasma membrane SNARE)
snap25 (plasma membrane snare)
synaptotagmin (vesicular Ca2+ binding protein)

Question 25

What is a SNARE?

Answer 25

a SNAP receptor

Question 26

What is the kiss-and-run model of synaptic vesicle recycling?

Answer 26

vesicles transiently fuse with the plasma membrane

after neurotransmitter release, the fusion pore is closed and the vesicles are recovered

Question 27

What is the clathrin-mediated endocytosis model of synaptic vesicle recycling?

Answer 27

a synaptic vesicle fuses and collapses into the membrane

a new vesicle is formed in a region distant from the fusion site

Question 28

What is the new model of synaptic vesicle recycling?

Answer 28

after a rapid internalization of the membrane via ultrafast endocytosis, the vesicle membrane is delivered to an endosome
clathrin-mediated regeneration of synaptic vesicles occurs at the endosome