lecture 8a - Synaptic function: Presynaptic

Question 1

The reticular theory

Answer 1

Until the late 1800s, the dominant theory was that nervous system was made up of a continuous mesh of nerve cell processes (e.g., axons and dendrites).

Question 2

The neuron doctrine

Answer 2

The nervous system is made up of individual, contiguous cells – neurons (rather than ‘continuous’).

Question 3

How do neurons communicate?

Answer 3

via synapses

Question 4

Presynaptic terminals (or boutons)

Answer 4

Neurons are connected to each other through synapses, sites where signals are transmitted in the form of chemical messengers.

Question 5

Synaptic vesicles

Answer 5

• Balls of lipid membrane (~40 nm in diameter)
• Contain a multitude of membrane bound proteins for:
  Filling vesicle with neurotransmitter
  Docking at presynaptic membrane
  Release of neurotransmitter
• Usually, an individual neuron will only release one type of neurotransmitter

i.e. a neuron will be ‘glutamatergic’, ‘GABAergic’, ‘dopaminergic’, etc.

Question 6

How do neurotransmitters get into vesicles?

Answer 6

• Transported by proton ‘antiporters’.
• An ATPase creates a proton gradient between the inside and the outside of the vesicle.
• Transporters use this gradient to drive the movement of neurotransmitters into vesicles by coupling the translocation of neurotransmitter to H+

Question 7

Action potentials trigger Ca2+ entry into presynaptic terminals…

Answer 7

which is critical for neurotransmitter release

Question 8

Action potentials trigger Ca2+ entry into presynaptic terminals release.

Answer 8

Question 9

Vesicle fusion with the presynaptic membrane is mediated by SNARE proteins

Answer 9

1. Synaptic vesicles move to the presynaptic active zone and dock at the plasma membrane.
2. Interaction between SNARE proteins on the vesicle and plasma membrane drive vesicle fusion.
3. Neurotransmitter is released into the synaptic cleft.

This process is Ca2+ dependent.

Question 10

Summary 2

Answer 10

Neurotransmitters are ‘packaged’ into synaptic vesicles.

Synaptic vesicles contain membrane bound proteins that allow docking, internalisation, and release of neurotransmitters.

Release of neurotransmitter is triggered by an increase in intracellular Ca2+.

Question 11

Simplified structure of a neuron

Answer 11

• A typical neuron receives synaptic input onto its dendrites and cell body.
• The axon is the ‘cable’ for information transmission.

Question 12

The Axon Initial Segment

Answer 12

• Action potentials are initiated at the axon initial segment (AIS).
• The AIS marks the boundary between a neuron’s somatodendritic and axonal compartments.
• The AIS contains a very high density of voltage-gated Na+ channels to enable action potential generation.

Question 13

Axons are complex structures

Answer 13

Question 14

Boutons terminaux

Answer 14

occur at the end of axons

Question 15

En passant boutons

Answer 15

occur along the length of the axons

Question 16

Summary 3

Answer 16

The axon is a neuron’s transmission ‘cable’.

Action potentials are initiated at the axon initial segment (AIS).

Synapses are located on boutons terminaux but also en passant boutons.

Question 17

Synaptic ‘probability of release’ (Pr)

Answer 17

• When an action potential arrives at a presynaptic bouton it does not always trigger the release of neurotransmitter.
• The likelihood of release occurring is stochastic (random) and is described by a parameter known as release probability, which ranges from 0 to 1.
• Release probability is not the same at all the synapses any given presynaptic neuron makes.
• At a single bouton, release probability is not fixed but is dynamic and changed by physiological factors

Question 18

Synaptic ‘probability of release’ (Pr) rules

Answer 18

If Pr goes up → synaptic strength goes up
If Pr goes down → synaptic strength goes down
If Pr = 0 → there is no synaptic communication

Question 19

Probability of release is stochastic

Answer 19

Question 20

Release probability is defined by a ratio

Answer 20

Question 21

Pr can be experimentally altered by:

Answer 21

1. Changing the extracellular Ca2+ concentration.
2. Applying blockers of presynaptic Ca2+ channels.
3. Activating presynaptic receptors (e.g., GPCRs) that alter Ca2+ channel activity.

Question 22

Summary 4

Answer 22

Action potentials do not always trigger neurotransmitter release.

The probability of release (Pr) is not the same at all the synapses a presynaptic neuron makes.

The probability of release can be altered by changing the presynaptic Ca2+ concentration.

Question 23

Short-term synaptic plasticity:

Answer 23

Short-lived changes in the strength of synaptic transmission…
…that reflect the prior experience / activity of the synapse.
Dynamic changes in release probability (Pr) underpin most forms of short-term synaptic plasticity

Question 24

An experimental example of short-term synaptic plasticity

Answer 24

Question 25

An experimental example of short-term synaptic plasticity -Hippocampal CA3-to-CA1 synapses

Answer 25

Question 26

Stimulate at low frequency:

Answer 26

stable synaptic responses

Question 27

Stimulate at higher frequencies:

Answer 27

- change in synaptic strength - Changes in paired-pulse ratio (PPR) are a measure of short-term synaptic plasticity

Question 28

Changes in paired-pulse ratio usually reflect brief changes in release probability

Answer 28

Question 29

Presynaptic terminals contain a ‘readily releasable pool’ of vesicles

Answer 29

Question 30

Short-term plasticity is determined by the number of vesicles released – it is presynaptic

Answer 30