Synapses allow signals to be transmitted between neurones, or between a neurone and an effector. The signal crosses the synaptic cleft as a chemical message, called a neurotransmitter.
- A synapse between two neurones that uses acetylcholine (ACh) as the neurotransmitter is called a cholinergic synapse.
- A synapse between a motor neurone and a muscle fibre is called a neuromuscular junction.
Structure of a Synapse
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
The detailed structure of a synapse and of a neuromuscular junction.
A synapse is the junction between two neurones, or between a motor neurone and an effector.
- Synaptic cleft — the tiny gap between the presynaptic and postsynaptic membranes.
- Presynaptic neurone — has a swollen ending called the synaptic knob, which contains synaptic vesicles filled with neurotransmitter. The synaptic knob also contains many mitochondria (to provide ATP for neurotransmitter synthesis and active transport).
- Postsynaptic membrane — has specific receptors that the neurotransmitter binds to.
- There are many different neurotransmitters. Synapses that use acetylcholine (ACh) are called cholinergic synapses.
Transmission Across a Cholinergic Synapse
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
The sequence of events involved in transmission across a cholinergic synapse in sufficient detail to explain:
- unidirectionality
- temporal and spatial summation
- inhibition by inhibitory synapses.
- An action potential arrives at the synaptic knob of the presynaptic neurone.
- This causes voltage-gated calcium ion (Ca²⁺) channels in the presynaptic membrane to open.
- Ca²⁺ ions diffuse into the synaptic knob down their concentration gradient.
- The influx of Ca²⁺ causes synaptic vesicles to move to the presynaptic membrane and fuse with it.
- The vesicles release ACh into the synaptic cleft by exocytosis.
- ACh diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane.
- This causes sodium ion (Na⁺) channels in the postsynaptic membrane to open (these open because ACh has bound to them).
- Na⁺ ions diffuse into the postsynaptic cell, causing depolarisation of the postsynaptic membrane.
- If the depolarisation reaches the threshold, an action potential is generated in the postsynaptic neurone.
- Acetylcholinesterase (AChE), an enzyme in the synaptic cleft, breaks down ACh (hydrolyses ACh). This stops the signal and prevents continuous stimulation.
- Ca²⁺ ions are actively transported back out of the synaptic knob.
Why is transmission unidirectional?
- Neurotransmitter vesicles are only found in the presynaptic neurone, so neurotransmitter can only be released from the presynaptic side.
- Receptors for the neurotransmitter are only on the postsynaptic membrane.
- So the signal can only travel in one direction across the synapse.
Excitatory and Inhibitory Synapses
- Excitatory synapses — the neurotransmitter causes depolarisation of the postsynaptic membrane, making it more likely to reach threshold and fire an action potential.
- Inhibitory synapses — the neurotransmitter causes hyperpolarisation of the postsynaptic membrane (the potential difference becomes more negative than the resting potential), making it less likely to fire an action potential.
Summation
Summation is the process by which the effects of multiple small depolarisations are added together to reach the threshold for an action potential. A single impulse may not release enough neurotransmitter to reach threshold on its own.
Spatial summation
- Multiple presynaptic neurones all connect to one postsynaptic neurone.
- They release neurotransmitter at the same time, and the combined depolarisation may be enough to reach the threshold.
- Some of these synapses may be inhibitory. If enough are inhibitory, the overall effect may not reach threshold, and no action potential is fired.
Temporal summation
- One presynaptic neurone fires multiple impulses in quick succession.
- Neurotransmitter accumulates in the synaptic cleft faster than it can be broken down by AChE.
- The combined effect of repeated neurotransmitter release may be enough to reach the threshold and trigger an action potential.
Cholinergic Synapse vs Neuromuscular Junction
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
A comparison of transmission across a cholinergic synapse and across a neuromuscular junction.
A neuromuscular junction (NMJ) is the synapse between a motor neurone and a muscle fibre (effector). It uses the same basic mechanism as a cholinergic synapse, but with some key differences:
- The neurotransmitter is ACh (same as a cholinergic synapse).
- The postsynaptic membrane (called the motor end plate) has junctional folds. These increase the surface area for more ACh receptors and more AChE.
- An NMJ is always excitatory, which means it always triggers muscle contraction. A cholinergic synapse can be either excitatory or inhibitory.
At a neuromuscular junction, ACh binds to receptors on the sarcolemma (the muscle fibre’s membrane). The depolarisation travels down the T-tubules and causes the sarcoplasmic reticulum to release calcium ions (see Skeletal Muscles).
The animation below shows the action at a neuromuscular junction (you should be able to notice a few differences from the cholinergic synapse, especially at the end).
Effects of Drugs on Synapses
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
Students should be able to use information provided to predict and explain the effects of specific drugs on a synapse. (Recall of the names and mode of action of individual drugs will not be required.)
You don’t need to memorise specific drugs, but you do need to predict and explain the effect of a drug from a description of how it works.
Types of drug action
-
Agonists — have a similar shape to the neurotransmitter, so they bind to and activate the postsynaptic receptors. Effect: the postsynaptic neurone is stimulated even without a nerve impulse, so the response is enhanced/continuous.
-
Antagonists — bind to the postsynaptic receptors but do not activate them, blocking the neurotransmitter from binding. Effect: the postsynaptic neurone is not stimulated, so transmission is blocked.
-
Inhibitors of neurotransmitter breakdown — prevent the enzyme (e.g. AChE) from breaking down the neurotransmitter. Effect: neurotransmitter remains in the synaptic cleft for longer, so the postsynaptic membrane is stimulated repeatedly/for longer.
-
Drugs that stimulate neurotransmitter release — cause more neurotransmitter to be released from the presynaptic neurone. Effect: more neurotransmitter in the synaptic cleft, so more receptors are activated and the response is enhanced.
Answering drug-effect questions
- Identify the step the drug affects (e.g. “inhibits voltage-gated Ca²⁺ channels”).
- Chain through the consequences — work through every downstream step, not just the final outcome. For example: less Ca²⁺ enters the synaptic knob → fewer vesicles fuse with the presynaptic membrane → less ACh released into the cleft → fewer receptors activated on the postsynaptic membrane → less Na⁺ influx / less depolarisation → fewer action potentials generated.
Try it: Drug Effect Simulator
How this topic is tested
This analysis is based on past paper data from 2017 to 2025. It is intended for interest only and is not predictive of what will appear in future papers.
- Tested in 6 of 9 years (2017–2025): 20 question parts worth 53 marks.
- 19th most-examined topic overall by marks, 3rd in Unit 6.
Marks by year
Most-tested spec points
- Transmission Across a Cholinergic Synapse: tested in 10 parts (31 marks)
- Effects of Drugs on Synapses: tested in 6 parts (17 marks)
- Structure of a Synapse & Neuromuscular Junction: tested in 3 parts (7 marks)
- Synapse vs Neuromuscular Junction: tested in 1 part (4 marks)
Also links to: The Mechanism of Muscle Contraction, ATP Hydrolysis, The Resting Potential.
Maths and practical skills
- Units and standard form (MS 0.1, 0.2): e.g. 2023 P2 Q2.3
- Percentages, ratios and fractions (MS 0.3): e.g. 2017 P2 Q10.1
Tips from examiner reports
What students commonly get wrong
- Vesicles fuse; acetylcholine diffusesWatch out: vesicles fuse with the presynaptic membrane and release acetylcholine. It's the acetylcholine that diffuses across the synaptic cleft, not the vesicles. 2024 P2 Q1.2 · 2020 P2 Q5
- Calcium ions enter the synaptic knobWatch out: say calcium ions diffuse into the synaptic knob (or presynaptic neurone). "Into the presynaptic membrane" or "into the synapse" isn't precise enough. 2023 P2 Q2.1
- Say "receptors", and say where they areWatch out: acetylcholine binds to receptors on the postsynaptic membrane (at a neuromuscular junction, the sarcolemma). Not "the muscle", and not an "active site". 2022 P2 Q7.3 · 2024 P2 Q1.2 · 2020 P2 Q5
- Sodium ions enter, causing depolarisationWatch out: don't stop at "sodium ion channels open". Say sodium ions enter the postsynaptic neurone, causing depolarisation. If threshold is reached, an action potential is produced. 2024 P2 Q1.2 · 2023 P2 Q2.1
- Fewer action potentials, not weaker onesWatch out: if less acetylcholine binds, there are fewer (or no) action potentials. Action potentials are all-or-nothing, so they're never "weaker". 2022 P2 Q7.3
- Summation: say what reaches thresholdWatch out: name the type (temporal or spatial), then explain that enough neurotransmitter is released, or enough sodium ions enter, to reach threshold. "More impulses" on its own isn't enough. 2022 P2 Q7.2
Exam Question Practice
At a cholinergic synapse between two neurones in the spinal cord, nerve impulses only pass in one direction.
Give two reasons why.
(2 marks)
Hint
Which neurone releases the neurotransmitter? Which membrane has the receptors for it?
Mark Scheme
- Only the presynaptic neurone releases acetylcholine (has vesicles of it) (1 mark)
- Only the postsynaptic membrane has acetylcholine receptors (1 mark)
Also accepted / rejected
Tips
- Only the presynaptic neurone releases acetylcholine, and only the postsynaptic membrane has receptors
- Vesicles alone, the refractory period or sodium ions don’t answer it, because both neurones have sodium ion channels
A single presynaptic neurone was stimulated four times in quick succession. Figure 1 shows the changes in membrane potential in the postsynaptic neurone.
Name and explain the type of summation shown in Figure 1.
(2 marks)
Hint
How many presynaptic neurones are involved in Figure 1? What builds up with each impulse until threshold is reached?
Mark Scheme
- Temporal summation (1 mark)
- Repeated impulses from one neurone in a short time release enough acetylcholine for the postsynaptic membrane to reach threshold (1 mark)
Explanation (not marked): Each impulse releases a little neurotransmitter, which causes a small depolarisation that isn’t enough on its own. The impulses arrive close together, so each depolarisation adds to the last before it fades, until threshold is reached and an action potential is produced.
Also accepted / rejected
Also accepted
- “Enough sodium ions enter to reach threshold” (point 2)
- Depolarisation, or an action potential, for reaching threshold (point 2)
Tips
- It’s temporal summation, which means repeated impulses from one neurone in a short time
- Explain what builds up. Enough acetylcholine is released, or enough sodium ions enter, to reach threshold. “Many impulses reach threshold” isn’t enough
GABA is a neurotransmitter released at some inhibitory synapses in the brain. When GABA binds to its receptors, the postsynaptic neurone becomes hyperpolarised.
Explain how hyperpolarisation makes it less likely that an action potential is produced in the postsynaptic neurone.
(2 marks)
Hint
What happens to the potential inside the postsynaptic neurone? What then has to happen before the threshold is reached?
Mark Scheme
- The inside of the postsynaptic neurone becomes more negative (the potential is below the resting potential) (1 mark)
- So more sodium ions must enter to reach the threshold for depolarisation (an action potential) (1 mark)
Also accepted / rejected
Also accepted
- A greater potential difference across the membrane (point 1)
- Na⁺ for sodium ions (point 2)
Not accepted
- “The potential difference decreases” (point 1)
Tips
- Say the inside of the postsynaptic neurone becomes more negative than the resting potential
- Then explain the effect. More sodium ions must enter to reach the threshold
- Write “sodium ions”, not just “sodium”. Sodium ions enter the neurone; they don’t leave it
What earns marks
- Explaining the more negative inside by chloride ions entering or potassium ions leaving
A nerve impulse arrives at a neuromuscular junction in the diaphragm, and acetylcholine is released from the motor neurone.
Describe the sequence of events, after acetylcholine is released, that leads to the muscle fibre being stimulated to contract.
Do not describe what happens after calcium ions are released in the muscle fibre.
(4 marks)
Hint
How does acetylcholine cross the gap, and where does it bind? Which ions then enter, and what does that cause? Which store inside the muscle fibre releases calcium ions?
Mark Scheme
The points must be in the right order (1 mark is lost if they are not).
- Acetylcholine diffuses across the synaptic cleft (1 mark)
- It binds to receptors on the sarcolemma (1 mark)
- Sodium ions enter, causing depolarisation (an action potential) (1 mark)
- Calcium ions are released from the sarcoplasmic reticulum (1 mark)
Also accepted / rejected
Also accepted
- “Postsynaptic membrane” for sarcolemma (point 2)
- Na⁺ for sodium ions (point 3)
- “Endoplasmic reticulum” for sarcoplasmic reticulum (point 4)
Not accepted
- “Sodium ion channels open” without saying that sodium ions enter (point 3)
Tips
- Start after acetylcholine is released, as the question says
- Acetylcholine diffuses across the cleft. The vesicles don’t cross it
- Say where the receptors are, on the sarcolemma (postsynaptic membrane), not just “on the muscle”
- Say that sodium ions enter, not just that channels open, and link this to depolarisation
- Calcium ions are released from the sarcoplasmic reticulum, not taken up by it. Stop there, as the question says
Glutamate is a neurotransmitter at many of the synapses that carry nerve impulses from pain receptors towards the brain. Pregabalin is a drug used to treat long-lasting nerve pain. Pregabalin binds to the calcium ion channels in the presynaptic neurone at some of these synapses, so fewer of the channels open.
Transmission at synapses that use glutamate is similar to transmission at synapses that use acetylcholine.
Explain how pregabalin reduces nerve pain.
(5 marks)
Hint
Start with what happens to the calcium ions. What do calcium ions normally trigger, and what follows at the postsynaptic neurone? Say what is reduced at each step.
Mark Scheme
Say what is reduced (no, fewer or less). An answer that only describes normal synaptic transmission scores max 4 marks.
- Fewer calcium ions enter the synaptic knob (1 mark)
- So fewer vesicles fuse with the presynaptic membrane, and less glutamate is released (1 mark)
- Less glutamate diffuses across the synaptic cleft (1 mark)
- Less glutamate binds to receptors on the postsynaptic membrane (1 mark)
- Fewer sodium ions enter the postsynaptic neurone, so fewer impulses are sent to the brain (1 mark)
Also accepted / rejected
Also accepted
- Ca²⁺ for calcium ions (point 1)
- “Presynaptic neurone” for synaptic knob (point 1)
- “Neurotransmitter” for glutamate (points 2 to 4)
- No depolarisation, or the threshold isn’t reached, for fewer impulses (point 5)
Not accepted
- “Presynaptic membrane” on its own for where calcium ions enter (point 1)
- “Signals” or “messages” for impulses (point 5)
Tips
- Say what is reduced at each step (no, fewer or less). Describing normal synaptic transmission only scores 4 marks
- Fewer calcium ions enter the synaptic knob, not the “synapse” or the “presynaptic membrane”
- Fewer vesicles fuse with the presynaptic membrane, so less glutamate is released and diffuses across the cleft
- Less glutamate binds to receptors on the postsynaptic membrane. Include both “receptors” and “membrane”
- Finish with fewer sodium ions entering the postsynaptic neurone, so fewer impulses reach the brain. Don’t stop at sodium ion channels opening
Also accepted