Synapses and Neurotransmission

What is a synapse?

The point at which electrical signals pass from one neurone to another (or to a muscle cell).

Why are synapses clinically important?

Many drugs (e.g. antidepressants, anaesthetics, muscle relaxants) act by modifying synaptic transmission.

How do neurones communicate at synapses?

Action potentials reach the presynaptic terminal

Neurotransmitter is released

The neurotransmitter generates a graded potential in the postsynaptic cell (excitatory or inhibitory).

What types of postsynaptic potentials exist?

• Excitatory postsynaptic potential

• Inhibitory postsynaptic potential

What is an electrical synapse?

A synapse where neurones are directly connected by gap junctions allowing ions to pass directly.

Key features of electrical synapses

• Gap junctions (~2 nm)

• Very fast transmission

• Faithful signal transfer

• Little modulation

What is a chemical synapse?

A synapse where neurones are separated by a synaptic cleft and communicate via neurotransmitters.

Key features of chemical synapses

• Presynaptic neuron

• Synaptic cleft

• Postsynaptic neurone

Electrical vs Chemical Synapses

What are three main anatomical types of synapses in the CNS?

• Axo-dendritic

• Axo-somatic

• Axo-axonal

What is found in the presynaptic terminal?

Synaptic vesicles clustered at active zones.

What is found in the postsynaptic membrane?

Clusters of neurotransmitter receptors and signalling proteins.

Outline the steps of neurotransmitter release

1. Neurotransmitters are synthesised and stored in vesicles

2. Action potential arrives at presynaptic terminal

3. Depolarisation opens voltage-gated Ca²⁺ channels

4. Ca²⁺ enters terminal

5. Vesicles fuse with membrane

6. Neurotransmitter released by exocytosis

7. Transmitter binds postsynaptic receptors

8. Postsynaptic response occurs

9. Transmitter removed (reuptake, breakdown, diffusion)

What criteria must a substance meet to be a neurotransmitter?

• Present in presynaptic neurone

• Synthesised there (enzymes present)

• Released by action potential

• Release is Ca²⁺dependent

• Specific receptors on postsynaptic cell

• Mechanism for removal or breakdown exists

How are neurotransmitters removed from the synaptic cleft?

1. Reuptake - Actively transporting back into the presynaptic axon terminal for reuse

2. Degradation

3. Diffusion away from the receptor site

4. Enzymatically transforming the neurotransmitters into inactive substances

What are the 4 main classes of neurotransmitters?

1. Amino acids

2. Amines (catecholamines, indoleamines)

3. Peptides

4. Purines

What is an ionotropic receptor?

A ligand-gated ion channel that produces fast responses.

What is a metabotropic receptor?

A G-protein coupled receptor (GPCR) that produces slower, modulatory responses.

What is the neuromuscular junction?

The synapse between a motor neurone and a skeletal muscle fibre.

Which neurotransmitter is used at the neuromuscular junction?

Acetylcholine (ACh).

What receptor does ACh act on at the NMJ?

Nicotinic acetylcholine receptor (ligand-gated ion channel).

Where is ACh used as a neurotransmitter?

Both the peripheral and central nervous systems.

ow is ACh synthesised?

In the presynaptic terminal by choline acetyltransferase (ChAT).

How is ACh broken down?

By acetylcholinesterase (AChE) in the synaptic cleft.

What 2 receptors does ACh act on?

• Nicotinic (ionotropic)

• Muscarinic (metabotropic)

What is the main excitatory neurotransmitter in the CNS?

Glutamate

What is the main inhibitory neurotransmitter in the CNS?

GABA

What does an EPSP do?

Depolarises the membrane, making an action potential more likely.

What does an IPSP do?

Hyperpolarises the membrane, making an action potential less likely.

What is temporal summation?

Addition of postsynaptic potentials occurring at the same synapse over time.

What is spatial summation?

Addition of postsynaptic potentials occurring at different synapses simultaneously.