Synaptic Transmission

Synapses are the junctions between neurones, or between neurones and effectors. They allow communication between cells using chemical messengers called neurotransmitters. Understanding synaptic transmission is essential for explaining how the nervous system integrates information, how drugs act, and how diseases of the nervous system arise.

Key Definition: A synapse is the junction between two neurones, consisting of the presynaptic membrane, the synaptic cleft (approximately 20 nm wide), and the postsynaptic membrane. Communication across the synapse is usually chemical, involving the release of a neurotransmitter.

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Structure of a Cholinergic Synapse

The most commonly studied synapse at A-Level is the cholinergic synapse, which uses acetylcholine (ACh) as its neurotransmitter. The key structures are:

Presynaptic Knob (Synaptic Bouton)

• Swollen end of the presynaptic axon.
• Contains many synaptic vesicles, each filled with approximately 10,000 molecules of acetylcholine.
• Rich in mitochondria — these provide ATP for the synthesis of ACh and for active processes such as the reuptake of choline.
• Contains voltage-gated calcium ion (Ca²⁺) channels in the presynaptic membrane.
• Contains enzymes for synthesising ACh: choline acetyltransferase catalyses the combination of choline and acetyl coenzyme A (acetyl CoA) to form ACh.

Synaptic Cleft

• A narrow gap of approximately 20–30 nm between the presynaptic and postsynaptic membranes.
• Contains the enzyme acetylcholinesterase (AChE), which is bound to the postsynaptic membrane and breaks down ACh after it has acted.

Postsynaptic Membrane

• Contains specific receptor proteins that are complementary in shape to acetylcholine.
• These receptors are ligand-gated Na⁺ ion channels — when ACh binds, the channel opens, allowing Na⁺ to enter the postsynaptic cell.

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The Sequence of Synaptic Transmission

The following steps describe transmission at a cholinergic synapse:

1. An action potential arrives at the presynaptic knob.

2. Voltage-gated Ca²⁺ channels open in the presynaptic membrane, and Ca²⁺ ions diffuse into the presynaptic knob down their concentration gradient.

3. Ca²⁺ causes synaptic vesicles to move to and fuse with the presynaptic membrane. The calcium ions bind to proteins on the vesicle surface, triggering exocytosis.

4. ACh is released into the synaptic cleft by exocytosis. Approximately 300 vesicles release their contents per action potential.

5. ACh diffuses across the synaptic cleft (this takes less than 0.5 ms due to the narrow width of the cleft).

6. ACh binds to specific receptors on the postsynaptic membrane. These receptors are nicotinic cholinergic receptors (named because nicotine can also bind to them).

7. The receptor changes shape, opening the associated ligand-gated Na⁺ channel. Na⁺ ions flow into the postsynaptic cell.

8. The postsynaptic membrane is depolarised, producing a local potential called an excitatory postsynaptic potential (EPSP).

9. If sufficient EPSPs summate to reach the threshold, an action potential is generated in the postsynaptic neurone.

10. ACh is hydrolysed by the enzyme acetylcholinesterase (AChE) in the synaptic cleft, producing choline and ethanoic acid (acetic acid).

11. Choline is reabsorbed into the presynaptic knob by active transport and recycled to synthesise more ACh using acetyl CoA from mitochondria.

12. Ca²⁺ is actively pumped out of the presynaptic knob, resetting the synapse.

Exam Tip: Learn this sequence thoroughly — exam questions frequently ask you to describe the events at a synapse in order. Always mention Ca²⁺ ions causing vesicle fusion, the role of acetylcholinesterase in removing ACh, and the recycling of choline.

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Excitatory and Inhibitory Postsynaptic Potentials

Excitatory Postsynaptic Potentials (EPSPs)