Synaptic Transmission

Action potentials cannot cross from one neurone to the next directly. Instead, every nerve impulse arriving at the end of an axon is briefly converted into a chemical signal, crosses a tiny gap, and is converted back into a new electrical signal in the next cell. These microscopic conversion stations are called synapses, and they are where the nervous system does much of its computation. This lesson covers the structure and function of the cholinergic synapse, in line with OCR A-Level Biology A specification module 5.1.3(h)–(i).

Key Definitions:

• Synapse — a junction between two neurones (or between a neurone and an effector) across which signals are transmitted chemically.
• Cholinergic synapse — a synapse that uses acetylcholine (ACh) as its neurotransmitter.
• Pre-synaptic membrane — the membrane of the neurone before the synapse.
• Synaptic cleft — the narrow (~20 nm) gap between the pre- and post-synaptic membranes.
• Post-synaptic membrane — the membrane of the next cell, studded with neurotransmitter receptors.
• EPSP / IPSP — excitatory or inhibitory post-synaptic potential; a small depolarisation or hyperpolarisation of the post-synaptic cell.

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Why Chemical Synapses Exist

You might ask: why don't neurones just link directly? There are two reasons:

1. Directionality. Chemical synapses only allow signals to flow one way (neurotransmitter is only stored in the pre-synaptic terminal and receptors are only on the post-synaptic cell). Electrical (direct) junctions would allow signals in both directions.
2. Integration. A single post-synaptic neurone receives input from hundreds or thousands of pre-synaptic neurones. Its decision to fire depends on summing excitatory and inhibitory inputs. This integrative computation is only possible at chemical synapses.

Chemical synapses therefore make the nervous system more than a simple set of wires: they make it a network capable of decision-making and learning.

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Structure of a Cholinergic Synapse

A cholinergic synapse has the following features:

• Pre-synaptic knob (terminal bouton): the swollen end of the axon, packed with mitochondria and smooth ER. ATP is needed in abundance for the synthesis, packaging and reuptake of neurotransmitters.
• Synaptic vesicles: small membrane-bound sacs (~40 nm diameter) containing ~10,000 molecules of acetylcholine each.
• Voltage-gated Ca²⁺ channels: in the pre-synaptic membrane; closed at rest.
• Synaptic cleft: ~20 nm wide, filled with extracellular fluid.
• Post-synaptic membrane: with nicotinic acetylcholine receptors, which are ligand-gated sodium channels.
• Acetylcholinesterase (AChE): an enzyme in the cleft or bound to the post-synaptic membrane that rapidly breaks acetylcholine down into choline and ethanoic (acetic) acid.

flowchart LR
    subgraph Pre-synaptic knob
    V[Vesicles with ACh]
    Ca[Voltage-gated Ca2+ channels]
    M[Mitochondria]
    end
    V -->|Exocytosis| C[Synaptic cleft]
    Ca --> V
    C --> R[Nicotinic ACh receptors]
    R --> PM[Post-synaptic membrane<br/>Na+ inflow → EPSP]
    C --> AE[Acetylcholinesterase<br/>hydrolyses ACh]
    AE --> CH[Choline + ethanoic acid]
    CH -.reuptake.-> V

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Step-by-Step Transmission

OCR expects you to describe the following sequence in detail.

1. Action Potential Arrives

An action potential travels down the axon and reaches the pre-synaptic knob, depolarising its membrane.

2. Voltage-Gated Ca²⁺ Channels Open

Depolarisation triggers voltage-gated calcium channels in the pre-synaptic membrane to open. Calcium ions — far more concentrated outside than inside — flow rapidly into the knob down their electrochemical gradient.

3. Vesicles Fuse with the Membrane

The influx of Ca²⁺ triggers vesicles containing acetylcholine to move to and fuse with the pre-synaptic membrane. Vesicles bind to SNARE proteins on the inside of the membrane; calcium acts on synaptotagmin, a calcium sensor, to bring about fusion. (You don't need to name SNAREs or synaptotagmin for OCR, but understanding that Ca²⁺ triggers fusion is essential.)

4. Neurotransmitter Released

Fusion opens the vesicle to the cleft and acetylcholine is released by exocytosis. It diffuses across the cleft (a few microseconds) to the post-synaptic membrane.

5. Receptors Bind ACh — EPSP Produced

Acetylcholine binds to nicotinic acetylcholine receptors, which are ligand-gated sodium channels. Binding opens them, and Na⁺ flows into the post-synaptic cell. This small depolarisation is called an excitatory post-synaptic potential (EPSP).

A single EPSP is typically too small to trigger an action potential on its own. Many EPSPs must sum (see below) to reach threshold.

6. Neurotransmitter Removed

Acetylcholine must be cleared from the cleft rapidly, otherwise every vesicle would trigger sustained stimulation and the synapse would be unable to produce distinct signals. This clearance is performed by acetylcholinesterase (AChE), which hydrolyses ACh into choline and ethanoic (acetic) acid.

7. Reuptake and Resynthesis