Synaptic transmission: basic principles

Question 1

Properties of electrical (gap junction) synapses

Answer 1

No delay
Two way
Little flex and plasticity
Not main role in brain (connexins can act as pore channels)

Question 2

Properties of chemical synapses

Answer 2

Short delay
One way
Great flexibility and plastic
Plays main role in the brain (pre/post synaptic terminal, synaptic vesicles, active zone, mitochondria)

Question 3

Chemical synapse depol and hyperpol

Answer 3

Na2+ into cell = depolarisation (excitation)

Cl- into cell = hyperpolarisation (inhibition)

Question 4

Steps of synaptic release

Answer 4

1- Docking
Involves snap-SNARE complex
v-SNARES on vesicle attach to t-SNARES on target membrane

2- Ca2+ entry
-AP causes depolarisation, opens Ca2+ channels, Ca2+ causes docked vesicles to fuse with membrane

3- Full fusion

• Fusion is triggered by influx of Ca2+ which binds to proteins of SNARE complex and changes conformation
• Energy to zip up SNARE complex from ATP hydrolysis
• Energy for pumping transmitter molecules into vesicles from proton gradient from vesicular H+-ATPase

4- Recycling
Pore opens, transmitter moves through diffusion

Question 5

Important features of Ca2+ dependent transmitter release

Answer 5

• Transmitter release requires binding of several Ca2+ ions
• Transmitter release mechanism prefers Ca2+ to other divalent cations Ca>Sr>Ba
• Release is stochastic in nature: Ca2+ increases probability of release but doesn’t guarantee release + release can occur spontaneously without AP or Ca2+ release

Question 6

How to visualise vesicular release

Answer 6

Using FM-dyes which is only visible in polar-hydrophilic environment

Question 7

Explain spontaneous release

Answer 7

Release of the neurotransmitter in the absence of presynaptic AP activates spontaneous synaptic responses, usually called miniature synaptic currents/potentials.
Typically each miniature response is triggered by single vesicle

Question 8

Explain how action potential increase release probability

Answer 8

m = p x N(ves) x N (syn)

So vesicular release of neurotransmitter is quantal
Quantal size = Amplitude of response produced by single vesicle

Amplitude = N(ves) x quantal size

Transmitter release is quantal in the CNS

Question 9

What are pools of synaptic vesicles known as?

Answer 9

Readily releasable pool (RRP)

Size of RRP limits the ability of AP’s to activate transmission

Question 10

Describe vesicle recycling

Answer 10

1- Coat subunits attach to membrane = coat assembly
2- Bud formation of coated region of membrane
3- Vesicle formation when dynamin forms collar around vesicle allowing it to bud off
4- Coat disassembles leaving an early endosome which are reformed into new vesicles filled with transmitter
5- Back to step 1

Question 11

Describe synaptic strength

Answer 11

Strength of synapse is expressed as average synaptic response triggered by the single AP
Presynaptic - mean quantal content which mainly depends on the release probability and total number of vesicles in the RRP

Postsynaptic - quantal size which depends mostly on the density of postsynaptic receptors to neurotransmitter and their efficiency

Question 12

Describe post-synaptic regulation

Answer 12

Postsynaptic density is densely packed with ion channels and other proteins = large multi-protein complexes
These can modulate function of ion channels and thereby alter synaptic strength usually by Ca2+ dependent phosphorylation and interaction with G-proteins and intracellular messengers

Question 13

Describe the Ribbon synapse

Answer 13

It is a conveyer belt of synaptic vesicles that underlies persistent high-frequency synaptic transmission